Production of a Low Molecular Weight Eosinophil Polymorphonuclear Leukocyte Chemotactic Factor by Anaplastic Squamous Cell Carcinomas of Human Lung

Goetzl, Edward J.; Tashjian, Armen H.; Rubin, Robert H.; Austen, K. Frank

doi:10.1172/jci108991

Cited by 54 publications

(15 citation statements)

References 23 publications

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“…Rather, what can be observed is a more general depressing effect on the basic migratory machinery of the PMN apparent in a persistent, extremely low random motility, a finding which has recently been confirmed with complement-activated serum as preincubation medium (32). Our observations do not exclude the existence of other mechanisms of deactivation, because, besides several studies reporting deactivation with relatively high doses of chemotactic factors (25,32,33), low-dose chemotactic deactivation has been found for other PMN (26) and eosinophil (34,35) chemoattractants. In analyzing the effect of different concentrations of N-formyl peptides on three established in vitro assay systems, which are thought to measure most essential PMN functions, support was gained for the concept that PMN hyperadhesiveness and chemotactic desensitation do not correspond with a general functional hyporesponsiveness of these cells.…”

Section: Resultscontrasting

confidence: 78%

“…Conversely, if these mechanisms are operating in circulating blood, e.g., in septicemia, granulocyte emigration to the inflammed focus may be impaired and bacterial dissemination facilitated. Furthermore, an analysis of the role of PMN adhesiveness in situations where in vivo chemotactic deactivation has been inferred as the cause of a chemotactic hyporesponsiveness (26,35,40) or in secondary granulocytopathies as exemplified by a recent case report of an juvenile peridontitis showing extremely spreaded PMN in vitro (41), may help to extend the clinical significance of these PMN surface characteristic.…”

Section: Resultsmentioning

confidence: 99%

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Modulating Influence of Chemotactic Factor-Induced Cell Adhesiveness on Granulocyte Function

Fehr¹,

Dahinden²

1979

J. Clin. Invest.

139

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A B S T R A C T The importance of adhesion in regulating locomotion and accumulation of polymorphonuclear leukocytes (PMN) has remained vague. We found that the chemotaxis of human PMN resuspended in heat-inactivated plasma was maximal toward 1-10 nM N-formyl-met-leu-phe (f-Met-Leu-Phe), but fell below random motility toward -100 nM. This impressive decrease of motility was paralleled by increased cell adherence on Petri dishes being minimal at 1 nM and maximal at >10 nM f-Met-Leu-Phe (6±1 and 37±2%[SE] adherent cells, respectively). Checked by phasecontrast microscopy, cells under stimulated adhesion lost the typical bipolar shape of moving PMN and became immobilized and highly flattened. PMN, preexposed to 250 nM f-Met-Leu-Phe and tested after washing, retained increased adhesiveness and showed extremely low random and chemotactic motility. In contrast, preexposure to 1 nM f-Met-Leu-Phe had no effect on chemotaxis. Supporting the concept that immobilizing hyperadhesiveness does not correspond to a general functional hyporesponsiveness of PMN, no depression of the initial ingestion rate was observed in the presence of 250 nM f-Met-Leu-Phe. Moreover, a close correlation was found between the induction of PMN adhesiveness and the stimulation of the hexose monophosphate pathway activity as well as of lysomal enzyme release (r -0.98). Thus, "chemotactic deactivation" and "high-dose inhibition of chemotaxis" by N-formyl peptides is the consequence of increased cell adhesiveness. This phenomenon provides a mechanism for cell trapping at the inflammatory site. Conversely, if operative in circulating blood, e.g., in septicemia, it may impair PMN emigration to such sites.This work was presented in part at a multidisciplinary ses-

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Section: Resultscontrasting

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Modulating Influence of Chemotactic Factor-Induced Cell Adhesiveness on Granulocyte Function

Fehr¹,

Dahinden²

1979

J. Clin. Invest.

139

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“…Circulating lymphocytes and total leucocyte counts were also compared with local eosinophil and macrophage infiltrations and listed in Table VI (Yoon, 1958) and may therefore not be coincidental. In contrast, combined local and peripheral eosinophilia in gastrointestinal (Yoon, 1958) and lung cancer (Goetzl et al, 1978) or peripheral eosinophilia alone in patients with various malignant tumours (Isaacson & Rapoport, 1946) are often signs of advanced disease, perhaps resulting from aberrant tumour products (Goetzl et al, 1978). However, we believe that local eosinophilia in early cancer could be associated with an immune response, e.g.…”

Section: R Nr R Nr R Nr R Nr R Nr R Nr R Nrr Nr R Nr R Nr R Nr R Nrmentioning

confidence: 79%

Local responses in primary and secondary human lung cancers. II. Clinical correlations

Kolb¹,

Müller²

1979

Br J Cancer

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“…Isoelectric focusing of AMCF demonstrated no chemotactic activity at these isoelectric points. A low molecular weight (300-400) chemotactic factor with preferential activity for eosinophilic polymorphonuclear leukocytes has also been isolated from extracts to bronchogenic carcinomas and a renal cell carcinoma metastatic to the lung (44). This factor differed from ECF-A derived from mast cells in that it eluted from Dowex-1 columns at pH 5.5 to 4.5 rather than 3.2 to 2.2.…”

Section: Discussionmentioning

confidence: 99%

Human Alveolar Macrophage-derived Chemotactic Factor for Neutrophils

Hunninghake¹,

Gadek²,

Fales³

et al. 1980

J. Clin. Invest.

216

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A B S T R A C T The presence ofneutrophils within the lung is a characteristic feature of a variety of lung diseases. To evaluate the potential role of alveolar macrophages in modulating the migration of neutrophils to the lung, normal human alveolar macrophages obtained from volunteers by bronchopulmonary lavage, were exposed for various periods of time in vitro to heat-killed microorganisms, and noninfectious particulates, immune complexes, and the macrophage supernates were evaluated for chemotactic activity. The microorganisms, noninfectious particulates, and immune complexes were chosen as stimuli for alveolar macrophages because these stimuli are representative of a spectrum of pathogenic agents that cause neutrophil accumulation in the lower respiratory tract. After incubation with each ofthese stimuli, alveolar macrophages released low molecular weight (400-600) chemotactic factor(s) (alveolar macrophage-derived chemotactic factor [s] [AMCF]) with relatively more activity for neutrophils than monocytes or eosinophils. Checkerboard analysis of the AMCF revealed that the factor was primarily chemotactic and not chemokinetic for neutrophils. The selectivity for neutrophils vs. monocytes could not be explained by a selective deactivation of monocytes, because the AMCF was more potent in deactivating neutrophils than monocytes. Partial characterization of AMCF demonstrated it was heterogeneous with the following features: (a) stable to heating at 56 and 100°C for 30 min; (b) stable over a pH range of 1.0 to 12.0 for 60 min; (c) stable after exposure to trypsin, papain, chymotrypsin, collagenase, and elastase; (d) partially inhibited by serum chemotactic factor inhibitor(s); (e) two major isoelectric points

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Production of a Low Molecular Weight Eosinophil Polymorphonuclear Leukocyte Chemotactic Factor by Anaplastic Squamous Cell Carcinomas of Human Lung

Cited by 54 publications

References 23 publications

Modulating Influence of Chemotactic Factor-Induced Cell Adhesiveness on Granulocyte Function

Modulating Influence of Chemotactic Factor-Induced Cell Adhesiveness on Granulocyte Function

Local responses in primary and secondary human lung cancers. II. Clinical correlations

Human Alveolar Macrophage-derived Chemotactic Factor for Neutrophils

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