Mediation of endothelial injury following neutrophil adherence to extracellular matrix.
Since polymorphonuclear leukocytes (PMN) rapidly migrate across the endothelial barrier and attach to extracellular matrix components, we tested the hypothesis that adhesion of PMN to matrix proteins can mediate endothelial injury following PMN activation. Studies were made using gelatin- and fibronectin-coated polycarbonate microporous filters (10 microns thick) on which confluent monolayers of bovine pulmonary microvessel endothelial cells were grown. PMN were layered either directly onto endothelial cells (at a ratio of 10:1) ("upright system") or onto gelatin- and fibronectin-coated filters with the endothelial monolayer grown on the underside of the filter without contact between PMN and endothelial cells ("inverted system"). PMN were activated with phorbol 12-myristate 13-acetate (PMA; 5 x 10(-9) M) in both systems. PMN activation increased endothelial permeability to 125I-labeled albumin in upright as well as inverted systems. Pretreatment of PMN with anti-CD18 monoclonal antibodies IB4 or R15.7, which inhibited PMN adherence to matrix constituents as well as to endothelial cells, prevented the permeability increase in both configurations. This effect of anti-CD18 monoclonal antibodies (mAbs) was not ascribed to a reduction in PMN activation, since PMA-induced superoxide generation was unaffected. We conclude that activation of PMN adherent to extracellular matrix proteins increases endothelial permeability to albumin and that this response is dependent on PMN adhesion to the matrix. The results support the concept that PMN-mediated increase in endothelial permeability is the result of "targeted" release of PMN products independent of whether the PMN are adherent to the extracellular matrix or the endothelium.
Kaslovsky
R A
RA
Department of Pediatrics, Albany Medical College of Union University, New York 12208.
Lai
L
L
Parker
K
K
Malik
A B
AB
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D018821:CD18 Antigens; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000293:injuries / Q000502:physiology* / Q000503:physiopathology; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D008833:Microcirculation / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011652:Pulmonary Circulation; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion; D013481:Superoxides; D013755:Tetradecanoylphorbol Acetate