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.
Suzuki
Kingo
K
Department of Biology, School of Education, Waseda University, Tokyo, Japan. kingo@kurenai.waseda.jp
Kobayashi
Nobuharu
N
Doi
Tomoko
T
Hijikata
Tomoko
T
Machida
Ikuko
I
Namiki
Hideo
H
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