Both group IB and group IIA secreted phospholipases A2 are natural ligands of the mouse 180-kDa M-type receptor

Snake venom and mammalian secreted phospholipases A(2) (sPLA(2)s) have been associated with toxic (neurotoxicity, myotoxicity, etc.), pathological (inflammation, cancer, etc.), and physiological (proliferation, contraction, secretion, etc.) processes. Specific membrane receptors (M and N types) for sPLA(2)s have been initially identified with snake venom sPLA(2)s as ligands, and the M-type 180-kDa receptor was cloned from different animal species. This paper addresses the problem of the endogenous ligands of the M-type receptor. Recombinant group IB and group ILA. sPLA(2)s from human and mouse species have been prepared and analyzed for their binding properties to M-type receptors from differ ent animal species. Both mouse group IB and group ILA sPLA(2)s are high affinity ligands (in the 1-10 nM range) for the mouse M-type receptor. These two sPLA(2)s are expressed in the mouse tissues where the M-type receptor is also expressed, making it likely that both types of sPLA(2)s are physiological ligands of the mouse M-type receptor. This conclusion does not hold for human group IB and IIA sPLA(2)s and the cloned human M-type receptor. The two mouse sPLA(2)s have relatively high affinities for the mouse M-type receptor, but they can have much lower affinities for receptors from other animal species, indicating that species specificity exists for sPLA(2) binding to M-type receptors, Caution should thus be exerted in avoiding mixing sPLA(2)s, cells, or tissues from different animal species in studies of the biological roles of mammalian sPLA(2)s associated with an action through their membrane receptors.