Hematological changes induced by C5a agonist peptides in mice

C5a has been implicated in early mobilization (15 to 30 minutes) induced by lipopolysaccharide (LPS) (Molendijk et al., 1986). This study examined the effects of response-selective C5a peptides on the hematological parameters in mice. The C5a peptides used were YSFKPMPLaR (I) and YSFKD(NMeNle)PlaR (II). A time course and dose response study using peptide I was performed in C5B1/6 mice. Mice were injected intravenously via the lateral tail vein with 0.1, 1 and 10 mg/kg peptide I. Control mice received saline. At 15, 30 and 60 minutes post-injection the mice were exsanguinated and the peripheral blood collected as well as bone marrow and spleen for determination of WBC, RBC, platelets, differentials and progenitor cells. No toxicity was noted. A time dependent and dose dependent neutropenia was seen with a maximum effect at 15 minutes post-injection with 10 mg/kg peptide I that returned to normal levels by 60 minutes. Interesting, the volume of blood obtained from the mice receiving peptide I was decreased at the early time points. No mobilization of progenitor cells was noted. Use of peptide II at 1 mg/kg for 15 and 30 minutes post-injection had no effect on the hematological parameters measured. Use of another strain of mouse (DBA/2) also showed no hematological effects of peptide I except doubling of circulating progenitor cells. C5a agonist peptide induced hematological effects were peptide and strain dependent.