IMMUNOREACTIVITY IN EOSINOPHILS FOR BOMBE SIN (B) AND SUBSTANCE-P (SP) - A NEW CONCEPT OF THE NEURO-IMMUNE AXIS

Immunoreactivity for B and SP was detected by means of light and elect ron microscopy (by preembedding immunocytochemistry), in eosiniphilic polymer-phonuclear leukocytes infiltrating the connective tissue of ga strointestinal and respiratory tract in mouse, rat and human; and in h uman bronchoalveolar lavages in case of hypereosinophilia. This positi ve reaction depends on the use of an acetic-acid-containing-fixative ( minimum 48 hours), and is located in the granules of eosinophils at th eir membrane level, and on eosinophil plasma membranes. Eosinophil per oxidases (catalases) should not affect the immunocytochemical reaction , since heating during a paraplast embedding and sodium-azide in elect ron microscopy procedure destroyed these enzymes. The membrane-bound i mmunoreaction for B and SP, with very dose structural similarity, sugg ested cross-reactivity between the two neuropeptides, with recognition of one or several epitopes by the polyclonal antisera. One of these e pitopes is probably associated with the C-terminal sequence of B (with tachykinin-like activity) and seems to be present in other neuropepti des such as SP; another epitope would be the N-terminal sequence of SP (with bradykinin-like activity). Hence, eosinophils could be the sour ce of tachykinin and bradykinin. Another hypothesis about the membrane immunolocalization (as yet unproved experimentally) would be a cross- reactivity due to recognition of electron-negative charges of membrane phospholipides. Lysophosphatidic acid could play a hormone-like activ ity and mimic B and SP activities, such as growth factors. Finally, an ti-B and anti-SP antisera could contain anti-idiotype antibodies uncov ering receptors. In conclusion : eosinophils might produce neuropeptid es or neuropeptide-like substances, with, for instance, bronchoconstri ctive activity by paracrine control and possible complementarity with nerve endings.