Human blood monocytes interact with type I collagen through alpha x beta 2 integrin (CD11c-CD18, gp150-95).
Human blood monocytes are attracted into connective tissues during early steps of inflammation and wound healing, and locally interact with resident cells and extracellular matrix proteins. We studied the effects of type I collagen on monocyte adhesion and superoxide anion production, using human monocytes elutriated from peripheral blood and type I collagen obtained from rat tail tendon. Both acid-soluble and pepsin-digested type I collagens promoted the adhesion of monocytes, whereas only acid-soluble collagen with intact telopeptides induced the production of superoxide. Adhesion and activation of monocytes on acid-soluble type I collagen depended on the presence of divalent cations. mAbs directed against integrin subunits CD11c and CD18 specifically inhibited adhesion and activation of monocytes on type I collagen. Protein membrane extracts obtained from monocytes were submitted to affinity chromatography on collagen I-Sepharose 4B, and analyzed by Western blotting using specific anti-integrin subunit Abs. In the case of both acid-soluble and pepsin-digested collagens, two bands were revealed with mAbs against CD11c and CD18 integrin subunits. Our results demonstrate that monocytes interact with type I collagen through CD11c-CD18 (alpha x beta 2) integrins, which promote their adhesion and activation. For monocyte activation, specific domains of the type I collagen telopeptides are necessary. Interactions between monocytes and collagen are most likely involved in the cascade of events that characterize the initial phases of inflammation.
Garnotel
R
R
Laboratoire de Biochimie Médicale et Biologie Moléculaire, Centre National de la Recherche Scientifique, UPRESA 6021, Institut Fedératif de Recherche 53-Biomolécules, Faculté de Médecine, Université de Reims Champagne-Ardenne, Reims, France.
Rittié
L
L
Poitevin
S
S
Monboisse
J C
JC
Nguyen
P
P
Potron
G
G
Maquart
F X
FX
Randoux
A
A
Gillery
P
P
D000143:Acids; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018845:CD11 Antigens / Q000502:physiology*; D018821:CD18 Antigens / Q000502:physiology*; D002413:Cations, Divalent / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D003094:Collagen / Q000378:metabolism / Q000502:physiology*; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016167:Integrin alphaXbeta2; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism / Q000502:physiology*; D011489:Protein Denaturation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000097:blood
D000143:Acids; D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D002413:Cations, Divalent; D016167:Integrin alphaXbeta2; D008562:Membrane Glycoproteins; D013481:Superoxides; D003094:Collagen; D004492:Edetic Acid