Protein Tyrosine Kinase but Not Protein Kinase C Inhibition Blocks Receptor Induced Alveolar Macrophage Activation

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 1993 Jan 1

PMID 18475548

Citations 1

Authors

K Pollock

M T Withnall

Affiliations

Soon will be listed here.

Abstract

The selective enzyme inhibitors genistein and Ro 31-8220 were used to assess the importance of protein tyrosine kinase (PTK) and protein kinase C (PKC), respectively, in N-formyl-methionyl-leucyl-phenylalanine (FMLP) induced generation of superoxide anion and thromboxane B(2) (TXB(2)) in guinea-pig alveolar macrophages (AM). Genistein (3-100 muM) dose dependently inhibited FMLP (3 nM) induced superoxide generation in non-primed AM and TXB(2) release in non-primed or in lipopolysaccharide (LPS) (10 ng/ml) primed AM to a level > 80% but had litle effect up to 100 muM on phorbol myristate acetate (PMA) (10 nM) induced superoxide release. Ro 31-8220 inhibited PMA induced superoxide generation (IC(50) 0.21 +/- 0.10 muM) but had no effect on or potentiated (at 3 and 10 muM) FMLP responses in non-primed AM. In contrast, when present during LPS priming as well as during FMLP challenge Ro 31-8220 (10 muM) inhibited primed TXB(2) release by > 80%. The results indicate that PTK activation is required for the generation of these inflammatory mediators by FMLP in AM. PKC activation appears to be required for LPS priming but not for transducing the FMLP signal; rather, PKC activation may modulate the signal by a negative feedback mechanism.

Citing Articles

Differential involvement of protein kinase C in activating cytosolic phospholipase A2 in alveolar macrophages and monocyte differentiated U937 cells.

Withnall M, Pennington A, Hagen M Inflamm Res. 1995; 44 Suppl 2:S139-40.

PMID: 8548367 DOI: 10.1007/BF01778301.

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