Ontogeny of the responsiveness to intravenous platelet-activating factor

Neonatal and young animals fail to devlop antigen-induced, lethal, systemic anaphylactic reactions. Recent evidence has documented that, in the adult rabbit, an unusual phospholipid autacoid, platelet-activating factor, induces almost all of the physiologic events associated with IgE-induced anaphylaxis. Thus, in the present study, the intravascular alterations after intravenous infusion of synthetic platelet-activating factor (1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine; AGEPC) into young rabbits were examined. In comparison to 13-week-old, adult rabbits, the intravascular infusion of > 1.0 μg/kg AGEPC was not lethal in rabbits of 8 weeks of age or less. In dose-response studies, the amount of AGEPC required to induce a lethal response in 50% of the animals tested (LD₅₀) was found to inversely correlate with age. In contrast, AGEPC-induced platelet aggregation in vitro was not affected by the age of the donor animal. Consistent with age-dependent platelet responsiveness in vitro, AGEPC-induced thrombocytopenia and intravascular accumulation of platelet factor 4 and thromboxane B₂ were also unaffected by animal age. Neutropenia and basopenia, as well as platelet and neutrophil sequestration in the pulmonary microvasculature after intravenous AGEPC infusion also were similarly unaffected by animal age. Although the mechanisms which modulate the profound and lethal physiologic responses following AGEPC infusion in the adult rabbit remain to be established, the current study clearly documents an age-dependent acquisition of systemic physiologic sensitivity to AGEPC and/or other mediators released as a result of intravascular AGEPC administration.