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HCC-1, a novel chemokine from human plasma
P Schulz-Knappe1, H J Mägert, B Dewald
1Lower Saxony Institute for Peptide Research (IPF), Hannover, Germany.
Insights
A novel CC chemokine, HCC-1, was identified in patients with chronic renal failure. This chemokine is constitutively expressed in normal tissues and enhances myeloid progenitor cell proliferation.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- CC chemokines are crucial regulators of immune cell function.
- Previous research has identified various CC chemokines with distinct expression patterns and activities.
- The role of specific chemokines in chronic renal failure and hematopoiesis requires further elucidation.
Purpose of the Study:
- To isolate and characterize a novel CC chemokine, designated HCC-1, from patients with chronic renal failure.
- To investigate the expression profile, receptor usage, and functional activities of HCC-1.
- To determine the effect of HCC-1 on myeloid progenitor cell proliferation.
Main Methods:
- Isolation of HCC-1 from hemofiltrate of patients with chronic renal failure.
- Molecular cloning of HCC-1 cDNA from human bone marrow.
- Sequence analysis and comparison with known CC chemokines.
- Assessment of HCC-1 expression in normal human tissues and plasma.
- Functional assays using human monocytes, T lymphocytes, neutrophils, eosinophils, and CD34+ myeloid progenitor cells.
Main Results:
- HCC-1, a novel CC chemokine (8,673 Da, 74 amino acids), was isolated and its cDNA cloned.
- Mature HCC-1 shares 46% sequence identity with macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta.
- HCC-1 is constitutively expressed in various normal tissues and present at high concentrations in plasma.
- HCC-1 exhibits weak activity on monocytes, inducing Ca2+ changes and enzyme release but not chemotaxis.
- HCC-1 enhances CD34+ myeloid progenitor cell proliferation, comparable to MIP-1 alpha but less potent.
Conclusions:
- HCC-1 represents a novel CC chemokine with a unique expression pattern and functional properties.
- HCC-1 plays a role in regulating monocyte responses and significantly enhances myeloid progenitor cell proliferation.
- Further research into HCC-1's specific roles in immune responses and hematopoiesis is warranted.
Abstract:
A novel CC chemokine, HCC-1, was isolated from the hemofiltrate of patients with chronic renal failure. HCC-1 has a relative molecular mass of 8,673 and consists of 74 amino acids including four cysteines linked to disulfide bonds. HCC-1 cDNA was cloned from human bone marrow and shown to code for the mature protein plus a putative 19-residue leader sequence. Mature HCC-1 has sequence identity of 46% with macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, and 29-37% with the other human CC chemokines. Unlike MIP-1 alpha and the other CC chemokines, HCC-1 is expressed constitutively in several normal tissues (spleen, liver, skeletal and heart muscle, gut, and bone marrow), and is present at high concentrations (1-80 nM) in plasma. HCC-1 has weak activities on human monocytes and acts via receptors that also recognize MIP-1 alpha. It induced intracellular Ca2+ changes and enzyme release, but no chemotaxis, at concentrations of 100-1,000 nM, and was inactive on T lymphocytes, neutrophils, and eosinophil leukocytes. In addition, HCC-1 enhanced the proliferation of CD34+ myeloid progenitor cells. It was as effective as MIP-1 alpha, but about 100-fold less potent.