Sequential maturation stages of monoclonal B lineage cells from blood, spleen, lymph node, and bone marrow from a terminal myeloma patient.

In order to fully understand the complexity of the monoclonal B lineage cells in multiple myeloma, it is necessary to evaluate the extent to which these cells are resident in solid lymphoid tissues and the phenotypic differences and similarities as compared to the circulating or bone marrow derived B lineage cells. Peripheral blood mononuclear cells from a patient with multiple myeloma were obtained 8 and 3 days prior to death, and mononuclear cells from lymph nodes, spleen, and bone marrow were obtained at autopsy. Rapid changes in the stage of differentiation of blood late-stage B lineage cells towards mature end-stage plasma cells were observed during the last week prior to death. Lymphoid cells within the blood comprised very few T cells, sub-normal numbers of monocytes, and 80% of B lineage cells which were at a late stage of differentiation. Shortly before death, plasma cells were found in the peripheral blood, indicating progression to plasma cell leukemia. At autopsy, the monoclonal B lineage cells in lymph node, spleen, and bone marrow represented different stages of terminal B cell differentiation. In each tissue, the B lineage cells were at an earlier differentiation stage, as defined phenotypically, than the circulating B lineage cells found in blood 3 days prior to death. Analysis of B cell markers and CD45 was used to define the differentiation stage of the relevant B cell populations, revealing a series of differentiation stages. The least mature B lineage cells (CD45hi) were found in lymph node. However, the CD45 isoform expressed was CD45R0, unlike most normal lymph node B cells. More differentiated B lineage cells (CD45med) were found in the bone marrow, and three sequential stages of pre-plasma cells were found in the spleen (CD45bright, CD45moderate, and CD45low-neg), all of which were CD45R0+. The B cells in normal spleen and bone marrow are CD45RA+. The presence of monoclonal B lineage cells in spleen was confirmed by Southern blotting. The B lineage cells from peripheral blood 3 days prior to death were approaching an end-stage plasma cell stage (CD45low/-). On B lineage cells from the various myeloma tissues, a concomitant loss of CD11b and increasing density of CD29 were observed as a function of progression to terminally differentiated stages.     

Increased tissue factor activity of monocytes/macrophages isolated from canine renal allografts

Kidney allografting was performed in a group of ten beagles, and viable leukocytes infiltrating the transplanted organs were isolated during episodes of acute rejection 5 or 6 days postoperatively. These infiltrate populations, consisting predominantly of lymphocytes and monocytes/macrophages, were found to have significantly increased amounts of procoagulant activity relative to control leukocytes isolated from circulating blood and lymph. Using nonspecific esterase staining in an agar microclot assay, procoagulant activity in the infiltrate leukocytes was found to reside in monocytes/macrophages rather than other coisolated cell types. By contrast, control monocytes from blood had no activity in this microclot assay. Procoagulant activity in the infiltrate cells was characterized as tissue factor. Increased amounts of this activator of the extrinsic pathway, as found in infiltrate monocytes/macrophages, may initiate clotting reactions and fibrin deposition within allografts.     

Growth of mouse megakaryocyte colonies in vitro.

Mouse bone marrow and spleen cells formed pure or mixed colonies of up to 80 megakaryocytes in agar cultures after stimulation by medium conditioned by activated mouse lymphoid cells. Megakaryocytes were identified on the basis of their morphology, polyploid mitoses and DNA content, and high cytoplasmic content of acetylcholinesterase. Megakaryocyte colony-forming cells were relatively small with a peak sedimentation velocity of 4.2 mm/hr. Spleen, lymph node, and thymus cells produced the factor stimulating megakaryocyte proliferation after culture in medium containing 2-mercaptoethanol, with or without added mitogens or allogeneic spleen cells. Peak activity in conditioning medium was associated with the small lymphocyte fractions in mouse spleen.     

Comparative Response of Normal Human Thymus and Lymph Node Cells to Phytohemagglutinin in Culture

Human thymocytes, in short-term tissue culture, show a proliferative activity distinct from that observed by either lymph node or blood lymphocytes.As expected, the behavior of lymph node lymphocytes in culture is very similar to that of peripheral blood lymphocytes. The only difference betweenthese 2 groups of cells was the finding of spontaneous proliferation by normal lymph node cells after 3 days in culture without phytohemagglutinin(PHA).

Whereas blood and lymph node lymphocytes show a negligible uptake ofH3T in the basal state, approximately 10 per cent of thymus cells incorporateH3T, indicating significant autonomous proliferation. This is unaffected byPHA and is unassociated with globulin synthesis as judged by immunofluorescent technics. After 3 days in culture, there are significantly more transformed cells and more cells which incorporate H3T into DNA in thymus cellcultures containing PHA than in the control cultures. However, the labelingindex of stimulated thymus cultures is less than either the basal rate of proliferation of thymocytes or 3-day cultures of PHA stimulated blood and lymphnode lymphocytes. These observations suggest that the normal human thymuscontains at least two populations of lymphoid cells: a major component whichshows autonomous and unsustained proliferative activity and does not respondto PHA, and a second and probably minor cellular component which transforms and proliferates in response to PHA.

Submitted on August 25, 1966 Accepted on October 24, 1966     

Prolactin receptor expression by lymphoid tissues in normal and immunized rats

Prolactin receptor (PRLr) expression and distribution in thymus, spleen, bone marrow, lymph nodes, and peripheral blood lymphocytes from young adult Lewis rats are analyzed using single-color flow cytometry and a well-characterized monoclonal antibody directed against the rat liver PRLr. The in vivo effects of regional immunization on PRLr expression are also examined. PRLr is found to be widely distributed among cells of the immune system and demonstrates lymphoid tissue-specific patterns of expression. Footpad immunization caused the rapid, but transient, induction of PRLr expression in the draining lymph node, with only modest effects on PRLr expression in other distant lymphoid tissues. These studies indicate that PRL may be capable of direct interaction with the immune system through differential expression of the PRL cell surface receptor on select lymphoid target cell populations.     

On the Origin of Foà-Kurloff Cells

The thymic and splenic release of Foà-Kurloff cells into the blood was studied in estradiol-treated male guinea pigs by comparison between the cellular content in afferent and efferent blood. The amount and distribution of such cells in thymus, spleen, lymph nodes, and bone marrow was investigated. The treatment with estradiol caused involution of the thymus and splenomegaly. An abundance of Foà-Kurloff cells was found in the red splenic pulp and a considerable release of such cells from the spleen into the blood was demonstrated. At the same time the output of lymphocytes from the spleen was reduced, suggesting that the Foà-Kurloff cells are transformed lymphocytes. The spleen contained an increased amount of erythroblasts, indicating a stimulation of splenic erythropoiesis by estradiol. In the bone marrow and the thymus the number of Foà-Kurloff cells was much smaller than in the spleen and no emigration of such cells from the thymus into the blood was demonstrated. A very small amount of Foà-Kurloff cells was found in the lymph nodes and very few occurred in the thoracic duct lymph. Thus, the Foà-Kurloff cells of the blood do not originate in the lymph nodes and do not recirculate between blood and lymph. It is concluded that the spleen is the major producer of Foà-Kurloff cells and that they are released from the spleen into the blood.     

Critical roles for IFN-beta in lymphoid development, myelopoiesis, and tumor development: links to tumor necrosis factor alpha

We have generated mice null for IFN-beta and report the diverse consequences of IFN-beta for both the innate and adaptive arms of immunity. Despite no abnormalities in the proportional balance of CD4 and CD8 T cell populations in the peripheral blood, thymus, and spleen of IFN-beta-/- mice, activated lymph node and splenic T lymphocytes exhibit enhanced T cell proliferation and decreased tumor necrosis factor alpha production, relative to IFN-beta+/+ mice. Notably, constitutive and induced expression of tumor necrosis factor alpha is reduced in the spleen and bone marrow (BM) macrophages, respectively, of IFN-beta-/- mice. We also observe an altered splenic architecture in IFN-beta-/- mice and a reduction in resident macrophages. We identify a potential defect in B cell maturation in IFN-beta-/- mice, associated with a decrease in B220+ve/high/CD43-ve BM-derived cells and a reduction in BP-1, IgM, and CD23 expression. Circulating IgM-, Mac-1-, and Gr-1-positive cells are also substantially decreased in IFN-beta-/- mice. The decrease in the numbers of circulating macrophages and granulocytes likely reflects defective maturation of primitive BM hematopoiesis in mice, shown by the reduction of colony-forming units, granulocyte-macrophage. We proceeded to evaluate the in vivo growth of malignant cells in the IFN-beta-/- background and give evidence that Lewis lung carcinoma-specific tumor growth is more aggressive in IFN-beta-/- mice. Taken altogether, our data suggest that, in addition to the direct growth-inhibitory effects on tumor cells, IFN-beta is required during different stages of maturation in the development of the immune system.     

Expression and kinetics of induced procoagulant activity in bovine pulmonary alveolar macrophages

Leukocytes, especially macrophages, are important cellular mediators of fibrin deposition and removal at tissue sites of inflammation. Pulmonary fibrin deposition is a prominent feature of bovine acute lung injury; therefore, we studied the resting and stimulated procoagulant responses of bovine pulmonary alveolar macrophages (PAM) and peripheral blood neutrophils (PMN). Freshly isolated normal PAM and PMN expressed negligible procoagulant activity. PAM stimulated with endotoxin lipopolysaccharide (LPS), 4 beta-phorbol 12-myristate 13-acetate (PMA) and bovine recombinant interleukin-1 beta (rBIL-1 beta) exhibited protein synthesis- and dose-dependent enhancement of procoagulant activity in 8-h cultures. Bovine recombinant granulocyte macrophage-colony stimulating factor (rBGM-CSF) and recombinant human gamma-interferon (rHIFN-gamma) did not induce procoagulant activity. The kinetics of LPS- and PMA-enhanced PAM procoagulant activity differed: LPS-induced enhancement developed earlier and more rapidly than PMA-induced enhancement. Pasteurella haemolytica LPS was more potent than Escherichia coli LPS in enhancing PAM procoagulant activity, while dexamethasone decreased both baseline and LPS- or PMA-stimulated activity by approximately 50%. PAM procoagulant activity resulted from tissue factor expression. Bovine PMN produced negligible procoagulant activity when stimulated, and are thus unlikely to be major contributors to procoagulant activity in bovine lung. Activity inhibitory to bovine tissue factor was present in both calf and adult sera, and was partly dependent on the presence of factor X for activity. Rapid induction of bovine PAM procoagulant activity by inflammatory mediators, and subsequent resistance to degradation, may thus combine to promote an alveolar microenvironment permissive to fibrin deposition in bovine acute lung injury.     

Effect of annexin-A1 peptide treatment during lung inflammation induced by lipopolysaccharide

Lung endotoxemia is characterized by neutrophil accumulation, increased vascular permeability and parenchymal injury. This can also affect the endogenous pathways that operate in the host to keep inflammation under control. Here, we demonstrate differential expression of annexin-A1 (AnxA1) protein in mice after the local or intraperitoneal administration of lipopolysaccharide (LPS; 1 mg/kg) in mice and the regulation of the endotoxemic inflammation after the pre-treatment with the AnxA1 peptidomimetic Ac2-26. The intranasal administration of LPS induced the leukocyte migration and cytokine release to the alveolar space, whereas the peritoneal administration of LPS generated a deregulated cellular and cytokine response, with a marked degree of leukocyte adhesion in the microcirculation. The peptide Ac2-26 pre-treatment inhibited the leukocyte migration and the pro-inflammatory cytokine release. Also, it induced the expression of endogenous AnxA1 and the anti-inflammatory cytokine IL-10. In conclusion, our data obtained from endotoxemia induced by local or intraperitoneal LPS administration suggested that the molecular mechanisms induced by AnxA1 peptidomimetic Ac2-26 lead to the regulation of leukocyte activation/migration and cytokine production induced by LPS.     

Circulation and migration of small blood lymphocytes in the rat: II. Study of the lymphocyte selective migration by light and electron microscopic autoradiography

Fourteen male Wistar rats were the recipients of labeled small lymphocytes (1.5 x 10(7) each) collected from the peripheral blood of syngeneic donors. The migrating labeled lymphocytes were traced in the various organs from one to 60 minutes following their transfusion. Sections from the lymph nodes, bone marrow, spleen, thymus, ileum, liver, lung, and kidney were analyzed morphologically by autoradiographic studies. The results showed that some of the labeled small blood lymphocytes migrate to the lymph node and bone marrow as early as one minute following transfusion; their exodus from these two organs occurs within three minutes. In the case of the spleen, the lymphocytes did not migrate selectively to the marginal zone of the lymphoid follicles until ten minutes following transfusion. The electron microscopic study of the spleen and lymph node showed that the labeled lymphocytes selectively migrate to certain areas which consist of reticulum cells, macrophages, unlabeled lymphocytes, and plasma cells. The term "immunocompetent zones" is proposed for these areas because of the biological significance of this selective migration with reference to immunity.     

Migration of Long-lived Lymphocytes to the Bone Marrow and to Other Lymphomyeloid Tissues in Normal Parabiotic Guinea Pigs

Guinea pigs, in which cells with longlife span were selectively labeled (³H-thymidine), were joined in parabiosisto nonlabeled syngeneic litter mates ata time when label reutilization detectable by radioautography could be excluded. The distribution of labeledcells was investigated quantitativelyusing radioautography and liquid scintillation counting in the marrow andblood at the time of establishment ofparabiosis and again at its termination2 wk later, when the thoracic ductlymph, lymph nodes, spleen, and thymus were also examined. Single animals labeled in the same mannerserved as controls. Of all cells with aslow rate of turnover and long lifespan, only small lymphocytes enteredthe circulation and crossed the anastomosis in detectable numbers. As indicated by the similar percentages oflabeling in respective tissues, a complete intermixing of long-lived lymphocytes occurred in the bone marrow,lymph, lymph nodes, and spleen of theparabionts. The sum of the per centlabeled lymphocytes in two parabiontswas in agreement with the extent oflabeling in respective tissues of singlecontrols. The presence of a minor population of lymphocytes with a long lifespan was confirmed in the marrow.Ten to 30 times as many labeled long-lived lymphocytes migrated into thebone marrow of initially unlabeled animals as were found in an equal volumeof blood. The majority, if not all long-lived lymphocytes migrate to the marrow from the blood, and they also reenter the blood. They have a similarlife span and in parabionts equilibratein a similar manner as recirculatinglong-lived lymphocytes.

Submitted on October 22, 1971 Revised on January 3, 1972 Accepted on January 4, 1972     

Amplification of the proliferative response to alloantigen by a factor present in an extract of syngeneic thymic lymphoid cells.

A synergistic interaction in the proliferative response to alloantigen has been previously noted when intact thymus cells are cultured with post-thymic (peripheral) lymphoid cells. In the present study, a factor extracted from the thymus has been shown to similarly enhance the reactivity of syngeneic lymph node cells and thus to retain the amplifier activity of intact thymus cells. The factor has no effect on lymphoid cell proliferation in the absence of alloantigen. Cells with amplifier activity are found in highest concentration in the thymus but also may be detected in spleen cells that are nonadherent to nylon wool. The factor is shown in these experiments to be derived from thymic lymphoid cells and to act primarily upon post-thymic (peripheral) lymphoid cells. As such, this factor appears to be distinct from various other thymus factors that have been localized to thymic reticuloepithelial elements and that are thought to effect predominantly the differentiation of T-cell precursors.     

Local abnormalities of coagulation and fibrinolysis and alveolar fibrin deposition in sheep with oleic acid-induced lung injury

Extravascular, primarily intra-alveolar, fibrin deposition is a histologic hallmark of acute lung injury in humans and experimental animals, but the mechanisms leading to this finding are poorly understood. To determine whether local abnormalities in the fibrinolytic-procoagulant balance contribute to alveolar fibrin deposition in acute lung injury, we studied bronchoalveolar lavage (BAL) fluids of anesthetized sheep that received intravenous oleic acid. Prominent alveolar fibrin deposition was observed within 2 h after oleic acid-induced lung injury. Procoagulant and fibrinolytic activities were determined in BAL samples of anesthetized, mechanically ventilated sheep before and 2 h after intravenous oleic acid or saline. BAL procoagulant activity was found to be due mainly to tissue factor associated with Factor VII. In baseline BAL samples, we found relatively low levels of procoagulant activity and relatively high levels of fibrinolytic activity. After induction of oleic acid-induced lung injury, the procoagulant activity of BAL was markedly increased, whereas fibrinolytic activity was either depressed or undetectable. Antiplasmin activity was detectable in BAL of sheep after oleic acid-induced lung injury, which contributed at least in part to the depressed fibrinolytic activity observed. These perturbations occurred with the appearance of extensive alveolar fibrin deposition. In control sheep, BAL fibrinolytic activity was decreased, and antiplasmin activity increased modestly after 2 h of mechanical ventilation, but procoagulant activity was unchanged and alveolar fibrin was not observed. Procoagulant activity in lung lymph and plasma after lung injury did not differ from baseline values, and fibrinolytic activity was undetectable in lymph or plasma samples. These data indicate that increased procoagulant activity and concurrent disruption of the balance of coagulation and fibrinolysis establish local conditions that promote acute fibrin deposition in the alveoli of mechanically ventilated, oleic acid-injured sheep.     

Increased in vitro and in vivo generation of procoagulant activity (tissue factor) by mononuclear phagocytes after intralipid infusion in rabbits

Intralipid, a fat emulsion widely used in parenteral nutrition, can produce marked functional changes of the mononuclear phagocyte system. We investigated the effect of Intralipid administration on the generation of procoagulant activity by rabbit mononuclear phagocytes. Two groups of ten rabbits given either a single infusion of Intralipid 10% or a similar volume of sterile saline were studied before and after infusion. Procoagulant activity was measured on isolated blood mononuclear cells after incubation with and without endotoxin, using a one-stage clotting assay. Cells from animals infused with Intralipid produced significantly more procoagulant activity than controls (P less than .01). Results were similar when freshly collected whole blood was incubated with and without endotoxin, and procoagulant activity was measured on subsequently isolated mononuclear cells (P less than .01). In addition, when rabbits were given a single injection of endotoxin, blood and spleen mononuclear cells harvested 50 to 60 minutes after the injection from animals pretreated with Intralipid expressed five to seven times more procoagulant activity than did cells from animals pretreated with saline. In all instances, procoagulant activity was identified as tissue factor. These findings suggest that Intralipid may cause functional changes in mononuclear phagocytes, resulting in increased production of tissue factor on incubation in short-term culture in vitro and in response to endotoxin in vivo.     

Crowding-dependent production of colony-stimulating factors by cultured syngeneic or allogeneic hematopoietic cells

Mitogenic stimulation in vitro of mouse T lymphocytes induces the production of the hematopoietic cytokines granulocyte-macrophage colony-stimulating factor and IL-3. The present experiments showed that simple crowding of murine spleen or lymph node cells was a sufficient inducing stimulus. Crowding did not have this consequence for thymus or marrow cells or spleen cells from nu/nu or Rag-1-/- mice lacking T lymphocytes. Crowding for as short a period as 24 h was sufficient to allow subsequent cytokine production in sparse cultures. Purified T lymphocytes also exhibited low levels of crowding induction of cytokine production and cytokine production was enhanced by IL-2 and IFN-gamma. However, IFN-gamma-/- spleen cells exhibited similar crowding-induced colony-stimulating factor production to that of control spleen cells. Excess cell crowding inhibited cytokine production. This inhibition was not caused by receptor internalization of cytokines but may contribute to the failure to observe IL-3 production in lymphoid organs in vivo. Coculture of allogeneic spleen or peritoneal cells was a strong inducing signal for colony-stimulating factor production but this parameter was unable to detect autoreactivity of T lymphocytes in mice that lack suppressor of cytokine signaling 1 and exhibit T lymphocyte activation.     

Prolonged Effects of Nitrogen Mustard on Mouse Haematopoietic and Lymphoid Tissues

Groups of mice have been autopsied at regular intervals during the period of lymphomyeloid tissue regeneration which follows the phase of hypocellularity induced by the i.v. injection of 100 μg (4 mg/kg bodyweight) nitrogen mustard. The marrow cellularity recovered to levels in the normal range by the 8th day and remained in this range up to the 40th day. Subsequently, the marrow showed a slight degree of hypocellularity up to day 120. Granulocytes were predominant during the initial phase of marrow regeneration from days 5–12. The thymus, lymph nodes, and spleen commenced regeneration during the second week post-injection. The thymus exhibited periodic size variations such that it was substantially larger than the thymus of age-matched controls from 20–30 d, 46–73 d, and 75–100 d after injection. The lymph nodes and lymphoid tissue of the spleen regenerated only slowly to reach control values by 40–50 d. Superimposed on the recovering lymphoid tissue of the spleen was a phase of erythroid hyperplasia lasting from 10–18 d post-injection. This coincided with a shift from granulocytosis to erythroid hyperplasia in the marrow. This erythroid hyperplasia lasted until day 30 when the cellular composition of the marrow and spleen returned to normal. A possible explanation of these results is that nitrogen mustard introduces a degree of synchrony into stem cell proliferation and differentiation. Additionally, these results emphasize the role of the haematopoietic microenvironment in the control of stem cell differentiation.     

Prolonged effects of nitrogen mustard on mouse haematopoietic and lymphoid tissues.

Groups of mice have been autopsied at regular intervals during the period of lymphomyeloid tissue regeneration which follows the phase of hypocellularity induced by the i.v. injection of 100 mug (4 mg/kg bodyweight) nitrogen mustard. The marrow cellularity recovered to levels in the normal range by the 8th day and remained in this range up to the 40th day. Subsequently, the marrow showed a slight degree of hypocellularity up to day 120. Granulocytes were predominant during the initial phase of marrow regeneration during the second week post-injection. The thymus exhibited periodic size variations such that it was substantially larger than the thymus of age-matched controls from 20-30 d, 46-73 d, and 75-100 d after injection. The lymph nodes and lymphoid tissue of the spleen regenerated only slowly to reach control values by 40-50 d. Superimposed on the recovering lymphoid tissue of the spleen was a phase of erythroid hyperplasia lasting from 10-18 d post-injection. This coincided with a shift from granulocytosis to erythroid hyperplasia in the marrow. This erythroid hyperplasia lasted until day 30 when the cellular composition of the marrow and spleen returned to normal. A possible explanation of these results is that nitrogen mustard introduces a degree of synchrony into stem cell proliferation and differentiation. Additionally, these results emphasize the role of the haematopoietic microenvironment in the control of stem cell differentiation.     

The Influence of Thymus Cells in Hemopoiesis: Stimulation of Hemopoietic Stem Cells in a Syngeneic, In Vivo, Situation

Using the spleen colony-forming techniqueto assay hemopoietic stem cells, (CFUs)experiments have been carried out to investigate the role of thymus cells in hemopoiesis. The experiments were carried outby injecting live or killed thymus cells intolethally-irradiated mice together withhemopoietic tissue containing CFUs. Theeffect of thymus cells on endogenouscolony formation in sublethally-irradiatedmice was also investigated. Colony formation by normal bone marrow or spleen isunaffected by the addition of thymus cells,but cell populations damaged by radiationall demonstrate increased colony numberswhen live thymus cells are injected within48 hr of initiating colony formation. Endogenous colony formation resulting from anx-ray dose of 475 red is increased 2.9times: exogenous colony formation frombone marrow or spleen populations whoseCFUs content has been reduced to approximately 20% of normal with 180-rad-rays is increased 2.1 times. Studiesinvestigating this enhancement demonstrate that at least some of the colonyforming cells require the cooperation oflive thymus cells. Under the conditions ofthese experiments, at least 10⁶ thymuscells must be injected to produce maximum enhancement.

Submitted on November 27, 1972 Revised on January 29, 1973 Accepted on February 16, 1973     

Abnormalities in pathways of alveolar fibrin turnover among patients with interstitial lung disease

Fibrin deposition is prominent in the histopathologic features of chronic interstitial lung disease. Human alveolar macrophages can potentially modulate this process because normal macrophages synthesize and express the initial enzymes of both coagulation and fibrinolytic pathways. In the present study, we examined the cell-associated procoagulant activity of macrophages lavaged from patients with sarcoidosis (n = 14) or idiopathic pulmonary fibrosis (n = 13) and compared the enzyme activities with that of a group of normal volunteers (n = 16). Cells from sarcoid patients had a mean (+/- 1 SD) tissue factor activity of 1,491 +/- 2,160 units/5 X 10(5) cells, as compared with a mean of 480 units (range, 140 to 1,000 units) for normal control subjects. The same cells had a mean plasma Factor VII equivalent of 4.7 ng/10(6) cells, as compared with 0.81 ng/10(6) cells (range, 0.2 to 2.0 ng) for the normal control subjects. The enhanced activity correlated with disease activity as judged by radiographic stage: only patients with Stage II or Stage III disease had consistently elevated procoagulant activity. There was no correlation of procoagulant activity with the percentage of lymphocytes in the alveolar fluid. Cells from patients with idiopathic pulmonary fibrosis also had increased tissue factor (mean, 2,980 +/- 2,619 units) but less consistently elevated Factor VII. There was considerable variation in both procoagulant activity and cell differentials between lavage sites in 10 patients in whom 2 separate lobes were studied concurrently. In addition, we examined the plasminogen activator (PA) activities of lavaged cells and concentrated alveolar fluids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alleles of the Ly-17 alloantigen define polymorphisms of the murine IgG Fc receptor.

Antibodies specific for allelic determinants of the cell membrane alloantigen Ly-17 were found to react with genetically determined polymorphic sites on the murine IgG Fc receptor (Fc gamma R). Monoclonal antibodies specific for Ly-17.2 and the Fc gamma R detected identical populations of cells in thymus, spleen, lymph node, and bone marrow and had nearly identical reactivity with a large number of hematopoietic neoplasms. Antibodies to the Fc gamma R and either allele of Ly-17 blocked binding of rabbit IgG dimers to the Fc gamma R on spleen and bone marrow cells. Antibodies to the Fc gamma R also blocked binding of antibodies to either allele of Ly-17, whereas anti-Ly-17 antibodies only partially blocked the binding of antibodies to the Fc gamma R. Biochemical studies showed that antibodies to Ly-17 and the Fc gamma R precipitated proteins of Mr 55,000-60,000. The identity of the proteins recognized by these antibodies was confirmed by sequential immunoprecipitation.