The levels and biologic action of the human neutrophil granule peptide HP-1 in lung tumors.
HP-1 is the most abundant human representative of a recently discovered class of neutrophil cystine- and arginine-rich peptides. These peptides have many potentially regulatory activities expressed at nanomolar concentrations. To establish the levels of HP-1 that can accumulate in human lung tumors and nondiseased lung fragments, tissues were extracted for their peptide content. The extracts were purified on reverse phase HPLC, and HP-1 and related peptides were identified by sequence analysis and their concentrations in the tissue quantitated by amino acid analysis. Immunohistochemistry was performed and strongly suggests that HP-1 is confined to granulocytes under most circumstances, and indicates that the levels of HP-1 measured in the tumors reflect the levels obtained when solid tissue is infiltrated by neutrophils. The maximum observed levels were 26 nanomoles per gram wet weight of tissue. Attempts were then made to correlate this level to the cytotoxic potential of HP-1 by performing in vitro cytotoxicity dose-response curves on several cell lines. Most cells were killed at between 1 and 8 microM, and the response depended on the growth conditions of the cells. The levels of HP-1 that accumulate in tumors can exceed the in vitro cytolytic concentrations. The levels are also considerably in excess of those required to exert in vitro regulatory actions.
Bateman
A
A
Royal Victoria Hospital, Departments of Medicine, Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada.
Singh
A
A
Jothy
S
S
Fraser
R
R
Esch
F
F
Solomon
S
S
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D001706:Biopsy; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000032:analysis* / Q000276:immunology / Q000494:pharmacology*; D002277:Carcinoma / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D023082:Defensins; D006098:Granulocytes / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry*; D008969:Molecular Sequence Data; D014018:Tissue Distribution; D023084:alpha-Defensins
D000596:Amino Acids; D001798:Blood Proteins; D023082:Defensins; D023084:alpha-Defensins; C406413:human neutrophil peptide 1