Identification of Selective Basophil Chemoattractants in Human Nasal Polyps as Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-2

Abstract

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 Ca2+ 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.

Can a panel of clinical, laboratory, and pathological variables pinpoint patients with sinonasal polyposis at higher risk of recurrence after surgery?

“…Judging from a review of the recent literature, to the best of our knowledge the present study is the first to find a direct association between serum basophils and CRSwNP recurrence rate (that was partly confirmed also by our tailored multivariate model). In 2004, Hartnell et al [21] investigated the mechanisms behind basophil recruitment from blood into tissues in human nasal polyp extracts. More recently, Mahdavinia et al [22] considered blood basophil counts within 6 months after surgery in 13 patients with CRSwNP, finding no statistical correlation between the blood basophil count and the number of basophils in the polyp tissue.…”

Matrix Metalloproteinase-19 Deficiency Promotes Tenascin-C Accumulation and Allergen-Induced Airway Inflammation

“…Tenascin-C accumulation has been detected in bronchial walls after allergen challenge and in chronic asthmatics (26)(27)(28). also displays the ability to cleave carriers proteins such as insulin-like growth factor binding protein-3 (IGFBP-3) that have been implicated in airway inflammation and tissue remodeling in asthma (29,30). MMP-19 is expressed in normal adult tissue, including the lung, supporting its role in normal tissue homeostasis (21,22).…”

Interaction of eosinophils with endothelial cells is modulated by prostaglandin EP4 receptors

“…Polymorphonuclear leukocytes (PMNLs, containing eosinophils and neutrophils) were isolated by dextran sedimentation of erythrocytes then by centrifugation on Histopaque gradients as described previously [51,52]. Eosinophils were purified from polymorphonuclear leukocyte using negative magnetic selection with an Ab cocktail (CD2, CD14, CD16, CD19, CD56, and glycophorin A) and colloidal magnetic particles from StemCell Technologies (Vancouver, Canada) [53].…”