Pulmonary edema induced by phagocytosing neutrophils. Protective effect of monoclonal antibody against phagocyte CD18 integrin.
We studied the changes in pulmonary hemodynamics and lung wet weight induced with opsonized zymosan (OZ) in isolated guinea pig lungs perfused with Ringer-albumin solution containing neutrophils (PMNs). Addition of OZ to the PMN-perfused lungs caused pulmonary vasoconstriction and weight gain; neither OZ nor PMNs added individually to the perfusate altered pulmonary vasomotor tone or wet weight. The steady gain in lung weight by 1,588 +/- 464 mg over the 45-minute study period was associated with pulmonary capillary hypertension and an increase in the capillary filtration coefficient, indicative of increased lung vascular permeability. These responses may not be due to generation of oxygen radicals, because the alterations in pulmonary hemodynamics and lung weight were not reduced by addition of superoxide dismutase, catalase, or superoxide dismutase plus catalase. We examined the basis of the PMN-mediated effects by layering PMNs on bovine pulmonary artery endothelial monolayers. Challenge with OZ resulted in increased endothelial permeability to 125I-albumin. The monoclonal antibody IB4 (directed against CD18, the common beta-subunit of structurally related adhesion receptors on phagocytes, LFA-1, Mac-1, and P150,95) prevented the OZ-mediated increase in PMN adherence to endothelial cells and the increase in endothelial permeability to 125I-albumin. IB4 also inhibited the lung weight gain mediated by the OZ-stimulated PMNs in intact lungs. The protective effect of IB4 could be ascribed neither to inhibition of uptake of OZ by PMNs nor to inhibition of release of oxygen radicals, myeloperoxidase, and elastase.(ABSTRACT TRUNCATED AT 250 WORDS)
Kaslovsky
R A
RA
Department of Pediatrics, Albany Medical College, Union University, NY 12208.
Horgan
M J
MJ
Lum
H
H
McCandless
B K
BK
Gilboa
N
N
Wright
S D
SD
Malik
A B
AB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology; D018821:CD18 Antigens; D002196:Capillaries / Q000503:physiopathology; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D016023:Integrins / Q000276:immunology*; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D009895:Opsonin Proteins / Q000494:pharmacology; D009929:Organ Size; D010587:Phagocytosis; D011654:Pulmonary Edema / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology*; D014661:Vasoconstriction; D015054:Zymosan / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D016023:Integrins; D009895:Opsonin Proteins; D016028:Receptors, Leukocyte-Adhesion; D015054:Zymosan