Human Nasal Polyp Epithelial Basophil/Mast Cell and Eosinophil Colony-stimulating Activity: The Effect is T-Cell-dependent

Abstract

We have previously reported highly potent basophil/mast cell (BMC) and basophil/eosinophil (Eo) colony-stimulating activities (CSA) in conditioned medium derived from cultured human nasal polyp epithelial scrapings (NP-CM). We now have examined the involvement of peripheral blood T-cells in the NP-CM stimulation of colony-forming units (cfu) from the blood of atopic and nonatopic subjects. Because the number of BMC- and Eo-cfu was significantly higher in cultures of peripheral blood from subjects with out-of-season ragweed allergic rhinitis than from control subjects (23.8 +/- 4.1 versus 9.0 +/- 2.4, p less than 0.01), we asked whether the observed colony stimulation could be a T-cell-dependent effect. Indeed, peripheral blood target cells consisting of a reconstituted mixture of T-cells and T-cell-depleted peripheral blood mononuclear cells (non-T-cells) yielded a significantly higher number of colonies in the presence of NP-CM than the non-T-cells alone. NP-CM did not stimulate colony formation by isolated T-cells. These observations point to interactions among nasal epithelial growth and differentiation factors, blood-borne progenitors and T-cells in the local accumulation of basophils, mast cells, and eosinophils in nasal polyps.

Hemopoietic Mechanisms in Allergic Airway Inflammation

“…Indeed, we have recently observed that both a serum hemopoietic factor, as well as an innate tendency for bone marrow responsiveness, can combine to contribute to ongoing inflammatory responses in the canine airway [38]. This further extends previous findings we have reported in patients with allergic rhinitis in which both the capacity of upper airway tissues to produce relevant hemopoietic growth factors, as well as increases in target circulating Eo/B progenitors, are critical in developing and maintaining an upregulation of hemopoietic responses in airway inflammation [16, 17, 18, 19, 20, 21]. …”

“…Inflamed tissues from patients with allergic rhinitis and nasal polyposis produce hemopoietic cytokines which promote the differentiation and maturation of CFU–Eo/B, as well as of mast cell progenitors; we have termed this tissue–driven response 'in situ hemopoiesis' [19, 20, 21, 22, 23, 24, 25]. …”

Structural Cell-Derived Cytokines in Allergic Inflammation

“…Specifically, allergic rhini tis nasal mucosal epithelial scrapings were shown to produce a higher colony-stimulating activity in vitro than normal nasal mucosal epithelial scrapings; this activity was most pronounced when supernatants of epithelial cultures from individuals with allergic rhi nitis were used to stimulate circulating (activated?) progenitor cell populations from this group of pa tients, as opposed to those from nonatopic subjects [14][15][16][17], Moreover, colony-stimulating activity was elabo rated in high amounts into supernatants of nasal mu cosal epithelial scrapings taken from excised polyp tissue prepared ex vivo [14,17]. In the context of doc umentation that both allergic rhinitis and nasal polyp tissues contain, throughout the epithelial and subepithelial-stromal levels, significant numbers of muco sal mast cells as well as (in the situation of polyps) activated eosinophils [18,19], these initial culture studies suggested that immature, inflammatory cell progenitors may be influenced locally by epitheliumand subepithelium-derived factors, among which were the hemopoietic colony-stimulating factors.…”

“…In the context of doc umentation that both allergic rhinitis and nasal polyp tissues contain, throughout the epithelial and subepithelial-stromal levels, significant numbers of muco sal mast cells as well as (in the situation of polyps) activated eosinophils [18,19], these initial culture studies suggested that immature, inflammatory cell progenitors may be influenced locally by epitheliumand subepithelium-derived factors, among which were the hemopoietic colony-stimulating factors. Moreover, T cell subpopulations present within the peripheral-blood compartment of polyp individuals also appeared to enhance the effect of epithelium-de rived colony-stimulating factors [14]. Lastly, in one important study, a highly enriched, low-frequency metachromatic cell progenitor could be shown to be resident within nasal polyp mononuclear cell popula tions [17].…”

Factors Influencing Basophilic Differentiation of HL-60 Cells

“…We have docu mented the existence of committed BMC progenitors in human peripheral blood [3,4] and found evidence for the contribution of hematopoietic mechanisms to allergic tissue inflammatory responses [6][7][8][9][10]. Among the cells which produce factors inducing human BMC growth and differentiation are T cells and allergic rhinitis or nasal polyp derived epithelium [6,7,9,10]; the precise identity of these factors has, however, re mained unclear.…”