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Differential effects of lipoxygenase products on FMLP and LTB 4 evoked neutrophil aggregation
Author(s) -
Beckman Jeffrey K.,
Gay James C.,
Brash Alan R.,
Lukens John N.,
Oates John A.
Publication year - 1985
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02534202
Subject(s) - chemistry , chemotaxis , arachidonate 5 lipoxygenase , endogeny , lipoxygenase , biochemistry , biophysics , enzyme , receptor , biology , arachidonic acid
There is evidence that the endogenous biosynthesis of LTB 4 is involved in the aggregation of human neutrophils induced by the chemotactic peptide f‐met‐leu‐phe (FMLP). If LTB 4 mediates this aggregatory response, then agents which desensitize neutrophils to LTB 4 should inhibit the cellular response to FMLP. Since many lipoxygenase products modulate other neutrophil responses to LTB 4 and FMLP, we have investigated the effects of lipoxygenase products on LTB 4 ‐ and FMLP‐initiated aggregation. Prior exposure to low concentrations of LTB 4 (0.5–10nM) inhibited subsequent aggregation to the same agent (50nM), but it did not influence the response to FMLP (10 −7 M). Relatively high concentrations of 5‐HETE (5–50μM) inhibited aggregation initiated by either stimulus. Although the hydroperoxy derivative 5‐HPETE also inhibited the response to LTB 4 , in the relatively narrow concentration range of 1–4μM it stimulated FMLP‐induced aggregation. This latter effect was confirmed using 12 cell preparations from six separate donors; it (the activity of 5‐HPETE) was not mimicked by other 5‐lipoxygenase products, including LTB 4 , nor the dihydroperoxide 8,15‐DiHPETE. Our results indicate that neutrophil aggregation in response to LTB 4 or FMLP can be selectively potentiated or inhibited. On the basis of these data we conclude that the endogenous synthesis of LTB 4 is not directly involved in the neutrophil aggregatory response to FMLP, although the hydroperoxy intermediate 5‐HPETE may act to enhance the cellular response.