Involvement of eicosanoids and surfactant protein D in extrinsic allergic alveolitis.

The pathophysiology of extrinsic allergic alveolitis (EAA) involves oxidative lung damage as well as interstitial and alveolar inflammation. Macrophages and mast cells are inflammatory components of EAA that produce both leukotrienes (LTs) and prostaglandin D2 (PGD2). In addition, PGD2 is also produced by the free-radical-catalysed peroxidation of arachidonic acid during oxidative stress. Urinary 8-iso prostaglandin F2alpha (8-isoPGF2alpha) and serum surfactant protein D (SP-D) are considered appropriate biomarkers of oxidative stress and interstitial lung disease activity, respectively. The present study aimed to assess the association of these biomarkers with the pathophysiology of EAA. Two cases of acute EAA caused by the inhalation of fungi spores were reported. Eight asthmatic patients and six healthy control subjects were also enrolled in the current study. The serum SP-D and urinary eicosanoid (LTE4, PGD2 metabolite (9alpha,11betaPGF2), 8-isoPGF2alpha) concentrations markedly increased during the acute exacerbation phase. These concentrations decreased following corticosteroid therapy in the EAA patients. There was a significant correlation between serum SP-D and urinary 9alpha,11betaPGF2 concentrations in the EAA patients. In conclusion, although the present study proposes that serum surfactant protein-D and urinary eicosanoids are new biomarkers involved in the various immunological responses in extrinsic allergic alveolitis, further large-scale studies are needed to investigate the role of these compounds, not just as biomarkers, but also as biological potentiators of extrinsic allergic alveolitis.     

Angiogenic Activity of Sera from Extrinsic Allergic Alveolitis Patients in Relation to Clinical, Radiological, and Functional Pulmonary Changes

Extrinsic allergic alveolitis (EAA) caused by inhaled organic environmental allergens can progress to a fibrotic end-stage lung disease. Neovascularization plays an important role in pathogenesis of pulmonary fibrosis. The aim of this study was to assess the effect of sera from EAA patients on the angiogenic capability of normal peripheral human mononuclear cells (MNC) in relation to the clinical, radiological, and functional changes. The study population consisted of 30 EAA patients and 16 healthy volunteers. Routine pulmonary function tests were undertaken using ERS standards. As an angiogenic test, leukocyte-induced angiogenesis assay according to Sidky and Auerbach was used. Compared with sera from healthy volunteers, sera from our EAA patients significantly stimulated angiogenesis (P < 0.001). However, sera from healthy donors also stimulated angiogenesis compared to PBS (P < 0.001). No correlation was found between serum angiogenic activity and clinical symptoms manifested by evaluated patients. A decrease in DLco and in lung compliance in EAA patients was observed but no significant correlation between pulmonary functional tests and serum angiogenic activity measured by the number of microvessels or an angiogenesis index was found. However, the proangiogenic effect of sera from EAA patients differed depending on the stage of the disease and was stronger in patients with fibrotic changes. The present study suggests that angiogenesis plays a role in the pathogenesis of EAA. It could be possible that the increase in the angiogenic activity of sera from EAA patients depends on the phase of the disease.     

外源性变应性肺泡炎的临床病理特征和影像学表现

目的探讨外源性变应性肺泡炎(EAA)的临床病理特征和影像学表现。方法分析5例外源性变应性肺泡炎病例的临床特点、影像学表现、肺活检的病理特征。结果 EAA常见的临床表现为咳嗽、呼吸困难、咳痰、发热;主要阳性体征为轻度紫绀、肺部听诊湿啰音或Velcro啰音;肺功能检查显示限制性通气功能障碍和弥散功能障碍。HRCT表现为磨玻璃影、小叶间隔增厚、小叶中心性结节、网格影和蜂窝肺等。支气管肺泡灌洗液显示淋巴细胞增多。肺活检组织病理学示淋巴细胞性间质性肺炎,细支气管周围可见小的不典型肉芽肿和多核巨细胞。患者对糖皮质激素治疗有效。结论临床表现结合影像学特点可提示EAA临床诊断,肺活检是诊断EAA有效的检查方法。     

Immunologically mediated aplastic anemia in mice: effects of varying the source and composition of donor cells

Experimental aplastic anemia (EAA) can be induced in CBA/J mice when they are sublethally irradiated and injected with lymph node cells (LNC) from C3H/He mice. Mice injected with LNC die of severe pancytopenia and marrow aplasia. In the present study, cells from other anatomical locations and subsets of LNC were examined for their ability to induce and to modulate EAA. Of peritoneal, splenic, and thymic cells, only cells from the thymus had EAA activity. C3H/He bone marrow cells did not induce any adverse effects in sublethally or lethally irradiated CBA/J mice. LNC, when depleted of B or phagocytic cells, retained EAA activity. In contrast, LNC depleted of T cells had significantly less EAA activity. Furthermore, when T cells of LNC were separated into peanut agglutinin (PNA)-receptor-positive and negative fractions, only the PNA- cells were able to induce EAA. EAA activity was lost when LNC were irradiated (1000 rad). The inability of splenic or bone marrow cells to induce EAA could have been due to the presence of cells that suppressed EAA activity. When splenic or bone marrow cells were coinjected with LNC, EAA was not induced. Coinjected irradiated splenic cells, but not bone marrow cells, were still able to inhibit EAA activity. Bone marrow cells seemed to inhibit EAA by replacing stem cells that were lost during the EAA process. On the other hand, splenic cells appeared to suppress EAA activity of LNC. Thus, radiosensitive PNA- T cells of lymph nodes or thymus were capable of inducing EAA, and their activity could be modulated by radioresistant splenic cells.     

Bile acid and pancreatic trypsin outputs are parallel during intraduodenal infusion of essential amino acids

There is disagreement as to whether contraction of the gallbladder occurs simultaneously with secretion of pancreatic enzymes during food ingestion. One study that employed exogenous cholecystokinin (CCK) alone showed dissociation of total bile acids (TBA) and trypsin outputs, while another study that employed exogenous CCK plus secretin showed parallel outputs of TBA and trypsin. Since previous studies have suggested that intraduodenal infusion of essential amino acids (EAA) evokes pancreaticobiliary secretion similar to that observed with food ingestion, we infused increasing doses of EAA intraduodenally in 10 subjects with intact gallbladder and in 10 subjects with previous cholecystectomy and measured total bile acids and trypsin outputs serially. In subjects with intact gallbladder, increasing molar doses of EAA induced parallel increases of TBA and trypsin outputs. In subjects with previous cholecystectomy trypsin outputs during infusion of EAA were similar to subjects with intact gallbladder, but their TBA outputs remained constant during the entire infusion period. Serial concentrations of plasma secretin did not change during intraduodenal infusion of EAA. These observations suggest that the gallbladder empties bile in concert with secretion of pancreatic enzymes following food ingestion.     

Some parameters of bronchoalveolar lavages in alveolitis

Eighty nine patients with alveolitis [60 with extrinsic allergic alveolitis (EAA) and 29 with idiopathic fibrosing alveolitis (IFA)] were followed up. Cytological and immunological studies of bronchoalveolar lavage revealed that the patients with EAA had elevated counts of lymphocytes, moderately increased neutrophils and eosinophils, decreased alveolar macrophages, elevated SIgA and T lymphocytes. In the patients with IFA, only higher counts of neutrophils were significant.     

The HRCT features of extrinsic allergic alveolitis

Exposure to organic dusts can produce an immune-mediated inflammatory response in sensitized individuals. The pulmonary disease caused by this response has been called extrinsic allergic alveolitis (EAA) or hypersensitivity pneumonitis. The clinical phases associated with this process have been termed acute, subacute, and chronic. There are corresponding imaging findings that are characteristic of each of these phases, although there is some overlap between the phases. The acute phase is characterized by confluent opacities that may mimic infection or edema. The subacute phase is characterized by centrilobular nodules, areas of ground-glass attenuation, a mosaic perfusion pattern, and air trapping on expiratory imaging. The chronic phase is characterized by subpleural irregular linear opacities with associated architectural distortion. Honeycombing may sometimes also be present. In the acute and subacute phases, the disease is predominantly in the lower lungs, whereas in chronic EAA the findings are predominant in the mid to upper lungs. Although the high-resolution computed tomography findings individually are nonspecific, the combination of the findings coupled with the distribution of the findings can often narrow the differential or allow a presumptive diagnosis of EAA to be made.     

Biochemical characteristics of fluid and cells of bronchoalveolar washings in patients with extrinsic allergic alveolitis

In 43 patients with exogenous allergic alveolitis (EAA), including 30 and 13 in its acute and chronic disease, bronchoalveolar lavage was performed, bronchoalveolar washing fluid (BAWF), isolated alveolar macrophages (AM) and unfractionated cellular sediment (NFCS) were separately studied. The BAWF showed high rates of lipid peroxidation (LPO), decreased antiproteolytic defense, and activated local synthesis of haptoglobin (Hp), fibronectin (FN), platelet activation factor (PAF), and enzymes of antioxidative defense (AOD). There was a rise in FN and PAF concentrations in the acute phase of the disease and higher PLO rates and elevated Hp levels in chronic EAA. The rate of oxidative metabolism in AMs was much higher in acute EAA than that in chronic EAA and accompanied by imbalance in the PLO-AOD system. AM levels of PAF was high in patients in both groups. The rate of LPO was higher in NFCS than in AM and was also followed by simultaneous AOD mobilization with preserved imbalance. A particularly significant AOD insufficiency in the NFCS was noted in chronic EAA, which was accompanied by decreased PAF. Thus, local pathochemical processes are of significance in developing the pattern of the process in EAA.     

N-methyl-D-aspartate receptor participates in neuronal transmission of photic information through the retinohypothalamic tract.

In order to assess the hypothesis that excitatory amino acids (EAA) are involved in the transmission of light information from retina to suprachiasmatic nucleus (SCN) and pineal via the retinohypothalamic tract (RHT), we have determined whether injections of EAA agonist into SCN could mimic the suppressive effects of light pulse on pineal melatonin production, and whether pretreatment with antagonists could block effects of light pulse in the intact rat. Injection of the EAA agonist N-methyl-D-aspartate (NMDA: 1.0 mM; 0.5 microliter) into the SCN suppressed plasma melatonin level and pineal N-acetyltransferase activity. The pretreatment with D-aminophosphonovalerate (D-APV: 2.5 or 10 mM; 2.0 microliters) or N-[1-(2-thienyl)-cyclohexyl]-piperidine (10 mM; 2.0 microliters) which are NMDA type receptor antagonists blocked the suppressive effect of the light pulse (3.0 Ix for 2 min), while the pretreatment with neither vehicle nor L-APV (optic isomer APV: 10 mM; 2.0 microliters) could block the effect of light. Alpha-D-glutamyl-amino-methylsulfonate (10 mM; 2.0 microliters or 25 mM; 2.0 microliters), which is a relative antagonist for non-NMDA type receptor, had no effect, either. These results suggest that EAA is involved in the transmission of light information through RHT and that in rat SCN EAA operates at the NMDA type receptor on the SCN.     

Liquid carbohydrate/essential amino acid ingestion during a short-term bout of resistance exercise suppresses myofibrillar protein degradation

A number of physiological events including the level of contractile activity, nutrient status, and hormonal action influence the magnitude of exercise-induced skeletal muscle growth. However, it is not the independent action of a single mechanism, but the complex interaction between events that enhance the long-term adaptations to resistance training. The purpose of the present investigation was to examine the influence of liquid carbohydrate (CHO) and essential amino acid (EAA) ingestion during resistance exercise and modification of the immediate hormonal response on myofibrillar protein degradation as assessed by 3-methylhistidine (3-MH) excretion. After a 4-hour fast, 32 untrained young men (18-29 years) performed a single bout of resistance exercise (complete body; 3 setsx10 repetitions at 75% of 1-repetition maximum; 1-minute rest between sets), during which they consumed a 6% CHO (n=8) solution, a 6-g EAA (n=8) mixture, a combined CHO+EAA (n=8) supplement, or placebo (PLA; n=8) beverage. Resistance exercise performed in conjunction with CHO and CHO+EAA ingestion resulted in significantly elevated (P<.001) glucose and insulin concentrations above baseline, whereas EAA ingestion only increased the postexercise insulin response (P<.05). Time matched at 60 minutes, the PLA group exhibited a peak cortisol increase of 105% (P<.001) with no significant change in glucose or insulin concentrations. Conversely, the CHO and CHO+EAA groups displayed a decrease in cortisol levels of 11% and 7%, respectively. Coinciding with these hormonal response patterns were significant differences in myofibrillar protein degradation. Ingestion of the EAA and CHO treatments attenuated 3-MH excretion 48 hours after the exercise bout. Moreover, this response was synergistically potentiated when the 2 treatments were combined, with CHO+EAA ingestion resulting in a 27% reduction (P<.01) in 3-MH excretion. In contrast, the PLA group displayed a 56% increase (P<.01) in 3-MH excretion. These data demonstrate that not only does CHO and EAA ingestion during the exercise bout suppress exercise-induced cortisol release; the stimulatory effect of resistance exercise on myofibrillar protein degradation can be attenuated, most dramatically when the treatments are combined (CHO+EAA). Through an "anticatabolic effect," this altered balance may better favor the conservation of myofibrillar protein.     

Excitatory amino acid neurotransmission evidence for a role in neuroendocrine regulation.

There is compelling evidence that endogenous excitatory amino acid neurotransmission is an important component of the neuroendocrine transmission line that regulates anterior pituitary-hormone release and, thus, reproduction. Excitatory amino acids (EAAs), such as glutamate and aspartate, are found in large quantities in neuroendocrine tissues such as the hypothalamus, and neurons from a variety of hypothalamic nuclei respond with marked excitation to EAA application. Exogenous EAA administration rapidly increases the release of GnRH, LH, and prolactin secretion in vivo and in vitro. Antagonist studies demonstrate that EAA-receptor activation is involved in a number of reproductive-endocrine events, such as the induction of puberty, seasonal breeding, steroid-induced LH secretion, and the preovulatory surge of LH and prolactin in the female. EAA regulation of these neuroendocrine events appears to be achieved through modulation and regulation of hypothalamic GnRH secretion.     

Mast cells, atypical lymphocytes, and neutrophils in bronchoalveolar lavage in extrinsic allergic alveolitis. Comparison with other interstitial lung diseases

Bronchoalveolar lavage (BAL) samples from exposed patients with extrinsic allergic alveolitis (EAA) contained mast cells in increased numbers in addition to lymphocytes. The counts rarely exceeded 0.5% in sarcoidosis, cryptogenic fibrosing alveolitis, or asbestosis or in control samples, but they were as much as 10-fold higher in EAA (p less than 0.001). Higher concentrations of histamine were demonstrated in EAA BAL-cell lysates, and histamine was released from cells challenged with anti-IgE. Electron microscopic examination confirmed that the cells were mast cells that differed from mast cells in dermal connective tissue and alveolar interstitial tissue but resembled bronchial subepithelial tissue mast cells in showing more features suggestive of activation. However, they showed more marked degranulation, and many were young. By light microscopy, they also resembled "mucosal" rather than "connective" tissue mast cells since granule staining was prevented by formaldehyde. Mast cell counts fell to normal after removal of patients from exposure, but lymphocyte increases, including atypical "blast" forms, persisted despite clinical recovery. Neutrophils were also increased before, but rarely after, removal. We suggest that EAA may provide an example of a human disease to support recent evidence that some delayed hypersensitivity disorders involve mast cells as well as lymphocytes.     

Production of soluble tumor necrosis factor receptors and tumor necrosis factor-alpha by alveolar macrophages in sarcoidosis and extrinsic allergic alveolitis

BACKGROUND: Alveolar macrophage (AM)-derived tumor necrosis factor (TNF)-alpha plays a pivotal role in the pathogenesis of sarcoidosis and extrinsic allergic alveolitis (EAA). The effects of TNF-alpha are mediated by membrane TNF receptor (mTNFR)-1 and mTNFR-2, and can be blocked by soluble TNF receptor (sTNFR)-1 and sTNFR-2. METHODS: We measured the production of the two sTNFRs and TNF-alpha in AM culture supernatants from 10 patients with active sarcoidosis, 12 patients with EAA, and 9 control subjects using an enzyme-linked immunosorbent assay method. RESULTS: Compared with control subjects, the spontaneous and lipopolysaccharide (LPS)-stimulated production of sTNFR-1, sTNFR-2, and TNF-alpha was significantly increased in patients with sarcoidosis and EAA. The concentrations of both sTNFRs, but especially of sTNFR-2, were closely related to those of TNF-alpha. The LPS-induced increase was 1.5-fold for sTNFR-1, at least fourfold for sTNFR-2, and at least 25-fold for TNF-alpha in all study populations. CONCLUSION: These results indicate that AMs can release the two sTNFRs in relation to TNF-alpha. sTNFR-2 may be more liable to shedding than sTNFR-1. Both sTNFR-1 and sTNFR-2 may be involved in the pathogenesis of sarcoidosis and EAA, possibly as counterregulators of TNF-alpha.     

Differential stimulation of muscle protein synthesis in elderly humans following isocaloric ingestion of amino acids or whey protein

To counteract the debilitating progression of sarcopenia, a protein supplement should provide an energetically efficient anabolic stimulus. We quantified net muscle protein synthesis in healthy elderly individuals (65-79 yrs) following ingestion of an isocaloric intact whey protein supplement (WY; n=8) or an essential amino acid supplement (EAA; n=7). Femoral arterio-venous blood samples and vastus lateralis muscle biopsy samples were obtained during a primed, constant infusion of L-[ring-2H5]phenylalanine. Net phenylalanine uptake and mixed muscle fractional synthetic rate (FSR) were calculated during the post-absorptive period and for 3.5 h following ingestion of 15 g EAA or 15 g whey. After accounting for the residual increase in the intracellular phenylalanine pool, net post-prandial phenylalanine uptake was 53.4+/-9.7 mg phe leg-1 (EAA) and 21.7+/-4.6 mg phe leg-1 (WY), (P<0.05). Postabsorptive FSR values were 0.056+/-0.004% h-1 (EAA) and 0.049+/-0.006% h-1 (WY), (P>0.05). Both supplements stimulated FSR (P<0.05), but the increase was greatest in the EAA group with values of 0.088+/-0.011% h-1 (EAA) and 0.066+/-0.004% h-1 (WY), (P<0.05). While both EAA and WY supplements stimulated muscle protein synthesis, EAAs may provide a more energetically efficient nutritional supplement for elderly individuals.     

Effect of smoking on the lipid composition of lung lining fluid and relationship between immunostimulatory lipids, inflammatory cells and foamy macrophages in extrinsic allergic alveolitis

Normal lung lining fluid suppresses lymphoproliferative responses. This effect is mediated by the major phospholipid components, but minor lipid components can stimulate lymphocyte proliferation. The aim of this study was to discover whether the changes in lung lipid composition reported in patients with extrinsic allergic alveolitis (EAA) might influence the levels of lymphocytes which occur in the lungs of these patients. Since cigarette smokers are less susceptible to EAA, we also investigated the effect of smoking on the lipid composition of lung lining fluid. Lung lining fluid was sampled by bronchoalveolar lavage (BAL) from 15 patients with EAA, and 9 non-smokers and 13 smokers without lung disease. The smoking controls had increases in phosphatidylethanolamine, sphingomyelin and phosphatidylglycerol, but lower levels of cholesterol and cholesterol:total phospholipid ratios compared with the nonsmoking controls. By contrast, the patients with EAA had increases in total phospholipid and sphingomyelin; there were no smoking related decreases in cholesterol; and several patients had levels of cholesterol and cholesterol:total phospholipid ratios above the upper limit for the controls. In the BAL fluids of the EAA patients, the levels.ml-1 of the immunostimulatory lipids sphingomyelin, phosphatidylethanolamine, cholesterol and cholesterol esters correlated with the number.ml-1 of lymphocytes, mast cells, neutrophils and "foamy" macrophages. Cholesterol levels (rs = 0.82) and lymphocyte counts (rs = 0.90) correlated most closely with "foamy" macrophages (p less than 0.001), suggesting that uptake of cholesterol by macrophages may enhance antigen-presenting function. These observations provide some support for the hypothesis that inflammatory reactions in the lungs might be influenced by the local lipid environment.     

Central nervous system control mechanisms of swallowing: A neuropharmacological perspective

Neuropharmacologicalin vivo andin vitro investigations are beginning to provide insight into chemical signaling processes within brainstem networks controlling the individual stages of swallowing. Different subtypes of excitatory amino acid (EAA) receptors operate at the level of solitarial interneurons programming the buccopharyngeal and esophageal stage, as well as motoneurons innervating esophageal striated musculature. Muscarinic cholinoceptors (MAChRs), probably activated via a propriobulbar input, are critically involved in generating output from solitarial neurons to esophageal motoneurons. Inhibition to tonically active GABA_A-receptor mediated afferents to solitarial premotor neurons results in rhythmic deglutitive output, reflecting disinhibition of EAA and MACK receptor activity. Motoneuronal EAA receptors may be regulated by a somatostatinergic input arising from solitarial premotoneurons. The available evidence is consistent with a transmitter heterogeneity in esophageal premotor neurons that may operate to provide chemical coding of afferents to the motor output stage of the pattern generator for esophageal peristalsis.     

Comparative analysis between dextran sulfate adsorption and direct adsorption of lipoproteins in their capability to reduce erythrocyte adhesiveness/aggregation in the peripheral blood

The purpose of this study was to compare the degree of erythrocyte adhesiveness/aggregation (EAA) reduction of two low-density lipoprotein (LDL) apheretic procedures, namely direct adsorption of lipoproteins (DALI) and dextran sulfate adsorption (DSA). A significant (P < 0.001) reduction of EAA was noted in six hypercholesterolemic patients who underwent a total of 40 apheretic sessions and no difference was noted in the degree of EAA reduction by the two techniques. Thus. being a real-time and point-of-care test, the erythrocyte adhesiveness/aggregation test can be applied in relevant situations of acute ischemia, where therapeutic LDL apheresis could improve the hemorheology of individuals with increased concentrations of cholesterol and inflammatory sensitive proteins.     

Cockade-like structures in alveolar macrophages in extrinsic allergic alveolitis

BACKGROUND AND OBJECTIVES: In immunocytochemical preparations of bronchoalveolar lavage (BAL) cells from patients with extrinsic allergic alveolitis (EAA), we observed the presence of alveolar macrophages with cockade-like structures in their cytoplasm (cockade+ alveolar macrophages). These cockade+ alveolar macrophages may reflect a subpopulation of alveolar macrophages which may show a different predominance in various interstitial lung diseases. In this study we aimed to compare the frequency of cockade+ alveolar macrophages in patients with EAA (n = 14) with the results obtained in patients with sarcoidosis (n = 11), idiopathic interstitial pneumonia (IIP; n = 10) and control subjects (n = 8). We also investigated the expression of the transferrin receptor CD71 on cockade+ alveolar macrophages. METHODS: In BAL fluid, the total number of cells and differential counts were determined, and immunocytologic examinations of macrophages and lymphocytes were done using monoclonal antibodies. The percentage of cockade+ alveolar macrophages was determined by counting 300 macrophages in the CD20 field of an immunocytochemical slide. RESULTS: The percentage of cockade+ alveolar macrophages was significantly higher in the EAA group (36 +/- 9%) compared to patients with sarcoidosis (12 +/- 5%) or IIP (11 +/- 10%) and control subjects (3 +/- 1%; p < 0.001). The proportion of CD71+ alveolar macrophages was significantly lower in EAA than in the other groups (p < 0.01), and the CD71 antigen was expressed on a significantly lower proportion of cockade+ alveolar macrophages compared to cockade- alveolar macrophages in EAA (p < 0.001). CONCLUSION: We conclude that cockade+ alveolar macrophages could play a role in the pathogenesis and differential diagnosis EAA.     

Effect of excising Freund''s adjuvant granuloma on subsequent development of experimental allergic arthritis.

Rabbits were immunized with antigen in Freund's complete adjuvant. Several weeks later the granuloma which developed was excised one day before joint challenge with antigen. The subsequent development of experimental allergic arthritis (EAA) was not affected, which argues against the chronicity of the disease being maintained by continuous recruitment of mycobacterial debris to EAA joints.     

Expression of the CD11/CD18 cell surface adhesion glycoprotein family and MHC class II antigen on blood monocytes and alveolar macrophages in interstitial lung diseases

The expression of molecules of the CD 11/CD18 cell surface adhesion glycoprotein family and HLA/DR antigen was studied on peripheral blood monocytes (PBM) and alveolar macrophages (AM) in bronchoalveolar lavage (BAL) fluid from patients with sarcoidosis, idiopathic pulmonary fibrosis (IPF), and extrinsic allergic alveolitis (EAA). Patients with these interstitial lung diseases showed increased numbers of macrophages in BAL fluid. This was probably caused by an increased influx of PBM to the alveoli since the numbers of cells with a monocytic morphology were also significantly increased in BAL samples from patients with interstitial lung disease, most prominently in IPF and EAA.The increased influx of PBM into the alveoli in patients with interstitial lung diseases was not reflected by an increased expression of the CD11/CD18 leukocyte function antigens on PBM.In healthy volunteers as well as in those with sarcoidosis, IPF, and EAA, the percentages of AM positive for CD11b (the C3bi complement receptor) and CD11c were lower than among PBM. This indicates that the expression of these cell surface adhesion molecules is downregulated during maturation and migration of PBM to the alveoli. The absolute numbers of AM positive for CD11b were increased in BAL fluid of IPF and EAA patients compared to healthy volunteers. EAA patients also showed increased absolute numbers of AM positive for CD11a and CD11c. This differentially increased expression of these leukocyte function antigens on AM suggests the influence of locally produced cytokines. Offprint requests to: H. C. Hoogsteden