Identification of selective basophil chemoattractants in human nasal polyps as insulin-like growth factor-1 and insulin-like growth factor-2.
In a search for novel leukocyte chemoattractants at sites of allergic inflammation, we found basophil-selective chemoattractant activity in extracts of human nasal polyps. The extracts were fractionated by reverse phase HPLC, and the resulting fractions were tested for leukocyte-stimulating activity using sensitive shape change assays. The basophil-selective activity detected was not depleted by a poxvirus CC-chemokine-binding protein affinity column. This activity was further purified by HPLC, and proteins in the bioactive fractions were analyzed by tandem electrospray mass spectrometry. Insulin-like growth factor-2 (IGF-2) was identified in these HPLC fractions, and the basophil-stimulating activity was inhibited by an anti-IGF-2-neutralizing Ab. Recombinant IGF-2 induced a substantial shape change response in basophils, but not eosinophils, neutrophils, or monocytes. IGF-2 stimulated chemokinesis of basophils, but not eosinophils or neutrophils, and synergized with eotaxin-1/CCL11 in basophil chemotaxis. IGF-2 also caused up-regulation of basophil CD11b expression and inhibited apoptosis, but did not stimulate degranulation or Ca(2+) flux. Recombinant IGF-1 exhibited similar basophil-selective effects as IGF-2, and both growth factors were detected in nasal polyp extracts by ELISA. This is the first demonstration of chemokinetic factors that increase the motility of basophils, but do not act on other granulocytes or monocytes. IGF-1 and IGF-2 could play a role in the selective recruitment of basophils in vivo.
Hartnell
Adele
A
Leukocyte Biology Section, Biomedical Science Division, Faculty of Medicine, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.
Heinemann
Akos
A
Conroy
Dolores M
DM
Wait
Robin
R
Sturm
Gunter J
GJ
Caversaccio
Marco
M
Jose
Peter J
PJ
Williams
Timothy J
TJ
D000595:Amino Acid Sequence; D001491:Basophils / Q000166:cytology / Q000502:physiology*; D048430:Cell Shape / Q000502:physiology; D002474:Cell-Free System / Q000502:physiology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000494:pharmacology; D002630:Chemotactic Factors / Q000302:isolation & purification* / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000302:isolation & purification* / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000302:isolation & purification* / Q000502:physiology; D008969:Molecular Sequence Data; D009298:Nasal Polyps / Q000378:metabolism* / Q000473:pathology; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation
C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002630:Chemotactic Factors; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II