Inhibition of Mg2+-dependent adhesion of polymorphonuclear leukocytes by serum hemopexin: differences in divalent-cation dependency of cell adhesion in the presence and absence of serum.
Circulating and nonadherent polymorphonuclear leukocytes (PMNs) become activated to attain adhesive state in an integrin-dependent manner by various stimuli, and perform a variety of microbicidal functions such as phagocytosis and superoxide production. We found that, in the absence of serum, a physiological concentration of hemopexin has a strong inhibitory action on Mg(2+)-dependent adhesion of PMA-activated PMNs to fibrinogen- and serum-coated surfaces. Under these conditions, Ca(2+) had no effect on Mg(2+)-dependent adhesion or the adhesion-inhibitory activity of hemopexin. In contrast, PMNs suspended in serum containing sufficient amounts of hemopexin to inhibit adhesion showed marked adherence, which was inhibited by EGTA. Next, we prepared a small-molecule fraction of serum by ultrafiltration followed by boiling. PMA-activated PMNs was found to adhere in the presence of both hemopexin and the small-molecule fraction, and the adhesion was enhanced by exogenous Ca(2+). EGTA abolished the effect of the small molecule fraction. The data suggest that serum contains adhesion-promoting factor(s) which allows PMNs to adhere despite the presence of hemopexin and that Ca(2+) is required for adhesion-promoting activity. Further study of hemopexin may provide clues for new therapeutic strategies aimed at interfering with PMN adhesion to control inflammation and tissue injury.
Department of Biology, School of Education, Waseda University, Tokyo, Japan. kingo@kurenai.waseda.jp
Kingo
K
Suzuki
Nobuharu
N
Kobayashi
Tomoko
T
Doi
Tomoko
T
Hijikata
Ikuko
I
Machida
Hideo
H
Namiki
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D016895:Culture Media, Serum-Free; D004533:Egtazic Acid / Q000737:chemistry; D005340:Fibrinogen / Q000378:metabolism; D006466:Hemopexin / Q000378:metabolism*; D008274:Magnesium / Q000097:blood*; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002413:Cations, Divalent; D016895:Culture Media, Serum-Free; D004533:Egtazic Acid; D005340:Fibrinogen; D006466:Hemopexin; D008274:Magnesium; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium