Elastin fragments attract macrophage precursors to diseased sites in pulmonary emphysema.

This study suggests one mechanism by which alveolar macrophages accumulate in the lung in pulmonary emphysema: elastin fragments generated at the diseased sites are potent chemoattractants for monocytes, the precursors of the macrophages. The most chemotactic elastin fragments have a molecular weight between 10,000 and 50,000 and are active at concentrations as low as 3 nanograms per milliliter. By comparison, elastin fragments with higher molecular weights and desmosines are active at concentrations greater than 0.3 microgram per milliliter. In addition, preincubation of monocytes with the 10,000- to 50,000-dalton elastin impairs the ability of the cells to migrate toward elastin fragments but not toward activated serum. Fragments of tropoelastin are not chemotactic for monocytes. Because elastin, but not tropoelastin, contains lysyl-derived cross-links, these structures may be the active chemotactic site on the elastin fragments.

Sampling theorem for rotationally symmetric systems based on Dini expansion.

A new formulation of the sampling theorem for circular apertures is proposed that uses a Dini series approach instead of a Fourier-Bessel one. The results obtained are especially convenient for the fast evaluation of pointspread functions: even the case of thin-ring aperture is not troublesome.

Maréchal intensity formula for small-Fresnel-number systems.

A simple modification of the known Maréchal intensity formula is proposed. It enables one to evaluate the near the-diffraction-focus intensity distribution for well-corrected optical systems with small Fresnel numbers of the focusing geometry. As an example, the focal-shift effect in perfect systems is briefly reexamined.

Maréchal intensity criteria modified for circular apertures with nonuniform intensity transmission: Dini series approach.

Starting with the Dini expansion of a wave aberration function, a relationship is derived between the Marechal evaluation of the Strehl definition (MESD) for uniformly illuminated aperture and the MESD for an aperture with nonuniform intensity transmission. The result is particularly useful for rapid evaluation of the far-field peak-intensity degradation due to aberrations and in problems connected with aberration balancing techniques, as well as for the estimation of optical system performance when the aperture intensity distribution is varied.

Fizeau digital interferometry with a diffraction-generated spherical wave for testing focusing optics.

A sufficiently small, reflective spherical particle at the focus of a test lens can replace the spherical autostigmatizing mirror in Fizeau digital interferometry, which is used for testing focusing optics. This small particle serves as a secondary coherent point source in the test arm and generates by diffraction a spherical wave that is used to produce the test beam. The relationships between the diffraction-generated wave and the size and shape of the diffracting element are discussed and also used to properly select the diffracting element. Experimental results confirm that the new technique has high accuracy.

Susceptibility to experimental interstitial lung disease is modified by immune- and non-immune-related genes.

To evaluate the concept that genetic factors modulate susceptibility to agents that cause interstitial lung disease, animal models of interstitial lung disease caused by bleomycin or by inhalation of organic particulates (ovalbumin or bovine gamma globulin after specific immunization) were studied in strains of mice with different genetic backgrounds. Because immune processes have been implicated in modulating the susceptibility to agents that cause interstitial lung disease, we also compared congenic, resistant strains (strains with the same background but with different H-2 haplotypes) for their sensitivity to the same agents. In bleomycin-induced disease, the degree of lung disease was different in some of the different strains of mice and, in some strains, was related to H-2 locus genes since all strains with H-2b haplotypes were high responders, whereas most of the strains with H-2a, H-2d, and H-2k haplotypes were low responders. However, some of the strains of mice with the same H-2 haplotype but otherwise different genetic backgrounds had different responses to bleomycin, suggesting that there is also a role for non-H-2 genetic factors in modulating the response to this experimental interstitial lung disease. In the ovalbumin-induced lung disease model, as in bleomycin-induced lung disease, there were different strain susceptibilities: 2 of the 3 strains in the H-2b group were high responders, as was 1 of the 3 strains in the H-2k group. Interestingly, evaluation of the congenic, resistant strains showed that on the same backgrounds the H-2-related genes were able to modulate the degree of lung lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse.

Evidence from divergent sources suggests that some forms of interstitial pulmonary disease are associated with abnormalities of the cellular immune system. To evaluate whether cellular immune processes are necessary determinants for the development of parenchymal alveolitis and fibrosis secondary to bleomycin, we examined the effect of bleomycin on the NIH, outbred white mouse as compared to the homozygous nude, athymic mouse on the NIH outbred background. The nude mouse has virtually no detectable cell-mediated immune function; we therefore hypothesized that if this component of the immune system were necessary for the development of bleomycin-induced interstitial disease, bleomycin would not induce the same pulmonary lesion in the nude mouse as in the white mouse. However, both white and nude mice developed alveolitis and fibrosis after intraperitoneal administration of bleomycin. Comparison of the frequency and severity of these lesions in the 2 groups revealed no significant differences. These findings suggest that the presence of an intact cell-mediated immune system is not an absolute requirement for the development of bleomycin-induced interstitial disease in the mouse. To the extent that this model is an appropriate approximation of human bleomycin-induced pulmonary disease, these results are consistent with the hypothesis that T-lymphocyte mediated processes are not primary determinants of this lesion.

Hereditary emphysema in the tight-skin mouse. Evaluation of pathogenesis.

The tight-skin (Tsk/+) mouse is a genetically determined model characterized by alveolar enlargement and physiologic evidence of emphysema. Morphologic evaluation of the lungs of these animals demonstrated increased numbers of potential protease-secreting cells (alveolar macrophages and neutrophils) in the lower respiratory tract prior to development of the emphysematous lesions. Quantitation of the neutrophils in the lungs of these animals was carried out by bronchoalveolar lavage. In the Tsk/+ mice, neutrophils constituted 3.5 +/- 2% of all inflammatory and immune effector cells present compared with 0.4 +/- 0.1% in control (+/+) mice (p less than 0.01). The Tsk/+ animals had no evidence of infection to explain the presence of the neutrophils and had normal proportions of lung T- and B-lymphocytes, suggesting that their lungs were immunologically normal. There was no evidence that the Tsk/+ mice have an antiprotease deficit; the capacity of serum of Tsk/+ mice to inhibit neutrophil elastase was no different from that of control +/+ animals. However, the fact that these animals have a persistent low level macrophage-neutrophil alveolitis prior to the development of the emphysematous lesion implies that the lung destruction may be associated, in part, with a chronic protease-antiprotease imbalance, similar to that hypothesized for human emphysema.

Hereditary emphysema in the tight-skin (Tsk/+) mouse.

The tight-skin (Tsk/+) mouse represents an autosomal dominant mutation characterized by increased thoracic size, large lungs, and a variety of abnormalities of loose subcutaneous connective tissue, cartilage, tendon, and bone. Because an increase in the size of the lung and thorax may result from destruction of alveolar walls and a loss of elastic recoil of the lung, the present study was undertaken to determine if the Tsk/+ mouse exhibits morphologic and physiologic characteristics of emphysema. In contrast to the lungs of normal mice, examination of the lungs of Tsk/+ mice by light and scanning electron microscopy revealed generalized enlargement of air spaces with numerous subpleural cysts and scattered bullae. In addition, many alveolar walls were either markedly thinned or broken and there was an increase in the number and size of the pores of Kohn. Consistent with these morphologic observations, the lungs of the Tsk/+ mice also exhibited physiologic characteristics consistent with emphysema. Compared to the lungs of normal mice, the lungs of Tsk/+ mice had a markedly increased total lung capacity of (1.8 +/- 0.1 ml versus 3.3 +/- 0.1 ml, p less than 0.001); compliance (0.077 +/- 0.006 ml/cm H2O versus 0.345 +/- 0.025 ml/cm H2O, p less than 0.001), and specific compliance (4.23 +/- 0.34% TLC/cm H2O versus 10.64 +/- 1.01% TLC/cm H2O, p less than 0.001). These findings suggested that the Tsk/+ mouse is a genetically determined model of emphysema that may be useful in determining the pathogenesis of destructive lung disease.