PMID- 8498524 OWN - NLM STAT- MEDLINE DCOM- 19930622 LR - 20181130 IS - 0002-9513 (Print) IS - 0002-9513 (Linking) VI - 264 IP - 5 Pt 1 DP - 1993 May TI - Effect of mode of activation of human eosinophils on tracheal smooth muscle contraction in guinea pigs. PG - L475-81 AB - We studied the relationship between mode of activation of isolated human eosinophils and in situ responsiveness in isolated tracheal smooth muscle (TSM) of guinea pigs. Human peripheral blood eosinophils were activated with either 10(-7) M phorbol myristate acetate (PMA) or 10(-6) M formyl-methionyl-leucyl-phenylalanine (fMLP) + 5 micrograms/ml cytochalasin B (CYB), and activation was confirmed by measurement of eosinophil peroxidase (EPO) secretion by kinetic assay. EPO secretion was similar after activation with fMLP+CYB (10.2 +/- 3.2% of total eosinophil content) and PMA (10.0 +/- 2.8% of total content; P = NS). Topical application of 6 x 10(6) eosinophils/cm2 activated with fMLP+CYB to the TSM segment caused 0.51 +/- 0.14 g/cm active tension (AT) in five preparations (P < 0.03 vs. baseline); cells activated with PMA caused no contractile response (0.04 +/- 0.03 g/cm AT, P = NS vs. baseline). Both PMA- and fMLP+CYB-activated cells caused augmentation of muscarinic responsiveness of guinea pig trachealis. The dose of intravenous acetylcholine required to cause a threshold response (ED0.3) was -7.3 +/- 0.1 log mol/kg at baseline vs. -8.7 +/- 0.5 log mol/kg after treatment with fMLP+CYB-activated eosinophils (P = 0.05) and -6.9 +/- 0.1 log mol/kg at baseline vs. -7.5 +/- 0.1 log mol/kg after PMA-activated cells (P < 0.01). Both AT and augmented muscarinic responsiveness were blocked by pretreating the eosinophils with 200 microM A-63162, an inhibitor of 5-lipoxygenase, before activation with fMLP+CYB. We demonstrate that eosinophils activated comparably (as assessed by EPO secretion) cause augmented muscarinic responsiveness and/or direct contraction of guinea pig TSM through secretion of a product of the 5-lipoxygenase pathway.(ABSTRACT TRUNCATED AT 250 WORDS) FAU - Strek, M E AU - Strek ME AD - Department of Medicine, University of Chicago, Illinois 60637. FAU - White, S R AU - White SR FAU - Hsiue, T R AU - Hsiue TR FAU - Kulp, G V AU - Kulp GV FAU - Williams, F S AU - Williams FS FAU - Leff, A R AU - Leff AR LA - eng GR - HL-02484/HL/NHLBI NIH HHS/United States GR - HL-32495/HL/NHLBI NIH HHS/United States GR - HL-46368/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Physiol JT - The American journal of physiology JID - 0370511 RN - 0 (Acetamides) RN - 0 (Lipoxygenase Inhibitors) RN - 0 (Phenyl Ethers) RN - 0452Y37YTA (N-hydroxy-N-(1-(4-(phenylmethoxy)phenyl)ethyl)-acetamide) RN - 11096-26-7 (Erythropoietin) RN - 3CHI920QS7 (Cytochalasin B) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - N9YNS0M02X (Acetylcholine) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Acetamides/pharmacology MH - Acetylcholine/pharmacology MH - Animals MH - Cytochalasin B/pharmacology MH - Eosinophils/drug effects/*physiology MH - Erythropoietin/blood/metabolism MH - Guinea Pigs MH - Humans MH - In Vitro Techniques MH - Kinetics MH - Lipoxygenase Inhibitors/pharmacology MH - Male MH - *Muscle Contraction MH - Muscle, Smooth/*physiology MH - N-Formylmethionine Leucyl-Phenylalanine/pharmacology MH - Phenyl Ethers MH - Tetradecanoylphorbol Acetate/pharmacology MH - Trachea/*physiology EDAT- 1993/05/01 00:00 MHDA- 1993/05/01 00:01 CRDT- 1993/05/01 00:00 PHST- 1993/05/01 00:00 [pubmed] PHST- 1993/05/01 00:01 [medline] PHST- 1993/05/01 00:00 [entrez] AID - 10.1152/ajplung.1993.264.5.L475 [doi] PST - ppublish SO - Am J Physiol. 1993 May;264(5 Pt 1):L475-81. doi: 10.1152/ajplung.1993.264.5.L475.