The effect of corticosteroids on monocyte and neutrophil activation in bronchial asthma

The expression of IgG (Fc) receptor (FcR) and complement receptor (CR) on peripheral blood monocytes and neutrophils was determined by the rosette technique in patients with asthma receiving different forms of treatment. In 31 patients taking inhaled therapy (i.e., bronchodilators alone or in combination with inhaled corticosteroids), monocyte FcR (48.19 +/- 1.24%, mean +/- SEM) and complement (66.54 +/- 1.09%) rosettes were significantly higher (FcR p less than 0.001, CR p less than 0.001) than in the 17 healthy, normal control subjects (FcR 37.94 +/- 0.82%, CR 59.7 +/- 0.98%). These increases in the percent rosettes between the two groups were observed even when a wide concentration range of IgG or complement was used to coat the red cells. No significant differences in monocyte receptor expression were observed between those patients being treated with bronchodilators alone or patients being treated in combination with inhaled corticosteroids. In 19 patients with asthma receiving oral corticosteroids, the mean monocyte FcR (38.21 +/- 1.73%) and CR (52.78 +/- 2.09%) were significantly reduced when these patients were compared with those patients receiving inhaled therapy alone (FcR p less than 0.001, CR p less than 0.001), and there was a significant inverse correlation between the percent rosettes and the dose of prednisolone. Neutrophil CR (51.32 +/- 1.30%, p less than 0.05) but not FcR expression (24.7 +/- 0.80%) was significantly increased when these were compared with those of control subjects (FcR 24.7 +/- 0.60%, CR 47.11 +/- 0.86%), and both neutrophil FcR and CR expression was significantly reduced (FcR p less than 0.01, CR p less than 0.001) in those patients with asthma receiving oral corticosteroids. (ABSTRACT TRUNCATED AT 250 WORDS)     

Cell-Surface-Marker Phenotyping in Patients with Leukemic Non-Hodgkin Lymphomas (NHL) of Low and Intermediate Malignancy

Certain markers for B lymphocytes (SIg, EAIgG, EAIgMC3b, EAIgMC3d, M-R) and T lymphocytes (E-R, EAIgG, EAIgM) were applied in order to characterize circulating neoplastic cells in non-Hodgkin lymphomas (NHL) of low and intermediate malignancy. In all cases, the diagnoses were based on the histological examination of lymph nodes, bone marrow, or skin biopsies. According to the Kiel classification, the diagnoses were as follows: chronic lymphocytic leukemia (CLL) n = 145. Immunocytoma (Ic) n = 39. Centrocytic (Cc) and centroblastic/centrocytic lymphoma (Cb/Cc) n = 17. Hairy-cell leukemia (HCL) n = 10. Prolymphocytic leukemia (PLL) n = 6 and Sézary's syndrome n = 3.In only 8 of the 220 cases did the leukemia cells show T characteristics. In leukemic B-cell lymphoma, a uniform phenotype was observed for B-CLL, characterized by a weak SIgm staining with or without SIgD, the presence of C₃d-receptors and a high percentage of M-R. This phenotype was also detected in one third of the cases of immunocytoma. The cells of BPLL and leukemic CC and CB/CC were characterized by a stronger SIg staining, a variable formation of complement receptors and, in most cases, absence of M-R. In all cases of B-cell lymphoma, the monoclonality of the cell proliferation could be confirmed by the restriction to a single L-chain type. This also applies to the 10 cases of HCL, although in the majority of these cases, several heavy-chain classes could be detected at the malignant cells.     

Human placental membrane receptor for IgG. Purification of the receptor and its subunit structure

The method of purification of the human placental Fc receptor to an active form is described. The FcR was purified from the glycoprotein fraction of the placental membranes by immunoprecipitation and chromatography on DEAE-cellulose. The purifield FcR corresponded to 1.5–2% of the protein present in the crude glycoprotein fraction (PGP) and showed the tendency to aggregate. In the presence of 1% SDS, 4 M urea or 5 M guanidine-HCl the placental FcR dissociated into subunits of molecular weight of 60,000–65,000. The 60,000–65,000 dalton glycoprotein subunits regarded as monomers of FcR are composed of two chains of molecular weight 25,000–30,000, linked by disulphide bonds. The subunits, after removal of dissociating agents, displayed IgG binding activity.     

Ligand inhibition studies on the role of Fc receptors in antibody-dependent cell-mediated cytotoxicity

Subjection of human peripheral blood lymphocytes to a temp shift from 4 to 37 degrees C resulted in a shedding of Fc receptors (termed FcRI) from 40-50% of FcR-positive cells followed by their re-expression within 4 hr; a phenomenon which had no effect on the cells' antibody-dependent killing capacity. Removal of lymphocytes having an immobile form of the Fc receptor resistant to the effects of the temp shift (termed FcRII), or removal of lymphocytes bearing both FcRI and FcRII, resulted in a similar amount of reduction in ADCC activity. This was attributed, therefore, to the loss of FcRII-positive cells. The influence of isolated (shedded) FcRI and Clq on ADCC activity was investigated. Soluble FcRI was shown to inhibit ADCC mediated through the immobile Fc receptors (FcRII), despite its lack of an ability to block EA rosette formation through these receptors. Clq also had a dose-dependent inhibitory effect on ADCC. These observations are consistent with earlier findings that FcRII possesses two active binding sites; and suggest that a prerequisite for killing in ADCC is the interaction of these with the C gamma 2 and C gamma 3 domains. The ability of synthetic peptides representative of human gamma 1-chain sequences to inhibit ADCC was determined, in an attempt to locate those sites within the IgG antibody Fc region involved in interaction with two FcR binding sites. Preliminary evidence was obtained to suggest that one of these is situated within the C gamma 2 domain, in the region of residues 274 (Lys)-294 (Glu).