Bovine melanoma growth stimulatory activity: a new monocyte-macrophage-derived cytokine of the IL-8 family. Partial structure, function, and expression in acute pulmonary inflammation.

Abstract

BACKGROUND:

Neutrophil-chemotactic peptides are a family of small basic peptides 70 to 80 amino acids in length. They contain four conserved cysteine residues, the first two spaced by one amino acid (C-X-C). The best characterized species is human IL-8. Other prominent members are melanoma growth stimulatory activity (GRO-alpha), neutrophil-activating peptide-2, and epithelial-cell derived neutrophil-activating protein 78.

EXPERIMENTAL DESIGN:

Bovine monocytes and alveolar macrophages were induced by lipopolysaccaride, and a major neutrophil chemotactic activity in the supernatant was purified by cation-exchange chromatography and reversed-phase HPLC. The chemotaxin was then analyzed for biologic activity on bovine neutrophils by in vitro chemotaxis, shape change, and transient rise of intracellular-free calcium concentration. The in vivo role of bovine GRO (boGRO) was tested immunohistologically in confirmed cases of pneumonic pasteurellosis.

RESULTS:

We have purified and partially sequenced a bovine homologue of human GRO-alpha. The partial amino acid sequence of boGRO was: APVVNELRCQCLQTLQGIHLKNIQSVKVTTPGP. BoGRO was biologically active and induced a dose-dependent neutrophil migration in the range of 10(-7) to 10(-9) M. BoGRO also induced a dose-dependent shape change in bovine neutrophils similar to human IL-8. This effect was detectable down to 10(-10) M. Similar effects were observed on the transient rise of intracellular-free calcium concentration. In bovine pneumonic pasteurellosis and, to a lesser extent, in normal lungs, immunoreactivity to human GRO was highly positive in hypertrophic type-II epithelial cells and in mesothelial cells, whereas pleural fibroblasts and bronchial epithelial cells were negative.

CONCLUSIONS:

BoGRO is a prominent neutrophil chemoattractant secreted by monocytes and alveolar macrophages. It is active at similar concentrations as human IL-8. The strong immunoreactivity in type-II epithelial and mesothelial cells of bovine pneumonia strongly suggest a role for boGRO in the genesis of pulmonary inflammation.

• Authors: C Rogivue, B D Car, I Allmann-Iselin, R D Zwahlen, A Walz
• Journal: Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 72 Issue 6 Pg. 689-95 (Jun 1995) ISSN: 0023-6837 [Print] United States
• PMID: 7783427 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CXCL1 protein, Bos taurus
• CXCL1 protein, human
• Chemokine CXCL1
• Chemokines
• Chemokines, CXC
• Chemotactic Factors
• Cytokines
• Growth Substances
• Intercellular Signaling Peptides and Proteins

Topics

• Acute Disease
• Amino Acid Sequence
• Animals
• Cattle
• Chemokine CXCL1
• Chemokines
• Chemokines, CXC
• Chemotactic Factors (chemistry, genetics, physiology)
• Chemotaxis, Leukocyte
• Cytokines (metabolism)
• Female
• Growth Substances (chemistry, genetics, physiology)
• Intercellular Signaling Peptides and Proteins
• Macrophages, Alveolar (metabolism)
• Molecular Sequence Data
• Monocytes (metabolism)
• Neutrophils (physiology)
• Pasteurella Infections
• Pneumonia (metabolism, microbiology)