Endothelial signal transduction system enhances neutrophil-induced pulmonary vascular permeability.
The mechanism by which stimulated polymorphonuclear leukocytes and neutrophils (PMNs) damage pulmonary vascular endothelium was investigated. The authors assessed the ability of unstimulated and mechanically stimulated PMNs to adhere to pulmonary endothelial cells and, thereby, alter pulmonary vascular permeability, measured as the pulmonary filtration coefficient (K) and haemodynamics. PMNs were stimulated by gentle agitation in a glass vial for 10 s. Perfusing lungs with the stimulated PMNs (n=6) resulted in significant accumulation of PMNs within the lungs, assessed by myeloperoxidase levels, and elicited a 4-fold increase in K and a 2-fold increase in pulmonary vascular resistance as compared to lungs perfused with unstimulated cells (n=6). The increases in K were completely blocked by GF109203X, a protein kinase C inhibitor (n=6); however, GF109203X only partially attenuated the increase in vascular resistance and had little effect on the accumulation of stimulated PMNs. An agonist of protein kinase C, phorbol myristate acetate, elicited dose dependent increases in both K and pulmonary vascular resistance even in the absence of PMNs (n=6). These findings indicate that the increases in pulmonary filtration coefficient and pulmonary vascular resistance induced by polymorphonuclear neutrophils result from endothelial cell injury mediated by activation of protein kinase C within the endothelial cells themselves.
Tanita
T
T
Dept of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Song
C
C
Kubo
H
H
Ono
S
S
Fujimura
S
S
D000818:Animals; D002199:Capillary Permeability / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D014655:Vascular Resistance
D009195:Peroxidase