Fibrin and fibrinogen degradation products with an intact D-domain C-terminal gamma chain inhibit an early step in accessory cell-dependent lymphocyte mitogenesis.
Although the low molecular weight degradation products of fibrinogen (FgDP) and fibrin (FbDP) are known to inhibit lymphocyte blastogenesis, the effect of purified macro-molecular FgDP and FbDP (molecular weight, 90 to 200 Kd) is unclear. We have examined the effect of these latter FgDP and FbDP and find that products that contain the D domain inhibit lymphocyte proliferation in response to T-cell mitogens, allogeneic mononuclear leukocytes, and anti-CD3 in vitro. Plasmic digestion of D1 in the absence of calcium with removal of the C-terminal end of the gamma chain or disruption of the gamma-gamma C-terminal cross-link site of D-dimer (DD) by puffadder venom (PAV-D) abrogates their inhibitory potential. Prior incubation of monocytes with DD or D1 inhibits subsequent lymphocyte transformation. Binding studies with radiolabeled DD and PAV-D confirm that monocytes interact only with DD. This specific binding may be competitively inhibited by monoclonal antibodies to CD11b/CD18 or by peptide analogues of the C-terminal gamma chain of fibrinogen that mimic the adhesion recognition site of integrins. We postulate that DD and D1 bind to CD11b/CD18 on adherent monocytes and modulate lymphocyte activation. These products are typically present in the plasma of patients with disseminated intravascular coagulation with sepsis and could therefore influence inflammatory processes in vivo.
Department of Medicine, University of Cape Town, Observatory, Republic of South Africa.
S C
SC
Robson
R
R
Saunders
L R
LR
Purves
C
C
de Jager
A
A
Corrigall
R E
RE
Kirsch
D000938:Antigen-Presenting Cells / Q000502:physiology*; D003208:Concanavalin A / Q000494:pharmacology; D005337:Fibrin / Q000737:chemistry*; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D005338:Fibrin Fibrinogen Degradation Products; D003208:Concanavalin A; D005337:Fibrin