Selective inhibition of T cell proliferation but not expression of effector function by human alveolar macrophages

BACKGROUND: Alveolar macrophages are thought to play an important part in regulating lung immune responses. While it is clear that human alveolar macrophages suppress T cell proliferation in vitro, the mechanisms by which this is achieved are not clear, nor is it known whether alveolar macrophages also inhibit other aspects of T cell function. METHODS: Peripheral blood mononuclear cells were stimulated with phytohaemagglutinin or house dust mite allergen, and cultured with variable numbers of autologous alveolar macrophages obtained by bronchoalveolar lavage from 20 normal subjects. RESULTS: Alveolar macrophages induced a reversible inhibition of T cell proliferation in response to both mitogen and allergen stimulation, with the latter being considerably more susceptible to inhibition. This was achieved via heterogenous mechanisms, involving both soluble factors derived from alveolar macrophages and cell-cell contact. Despite inhibiting proliferation, alveolar macrophages had little or no effect on T cell calcium flux, the characteristic changes in CD3, CD2, CD28 and interleukin-2 (IL-2) receptor expression which accompany normal T cell activation, and IL-2 and interferon gamma secretion. In contrast, alveolar macrophages inhibited the tyrosine phosphorylation of proteins which may be involved in IL-2 receptor-associated signal transduction. CONCLUSIONS: The immunoregulatory properties of alveolar macrophages are relatively selective, allowing T cell activation and cytokine secretion while inhibiting T cell proliferation within the lung.


     

A district urinary catheter policy. Why have one?

A catheter audit was performed at the Central Manchester Trust, which found that there was excessive ordering, inappropriate catheter selection by size, materials, balloon size and poor guidelines on catheter storage. From these findings and from the available literature, we have proposed guidelines on catheter selection with the aim of offering the best patient care and to provide cost efficiency which may be of benefit to other hospitals.     

Experimental axonopathy induced by immunization with campylobacter jejuni lipopolysaccharide from a patient with guillain‐barré syndrome

Campylobacter jejuni (C. jejunj) infection is the most common antecedent in the axonal variant of Guillain‐Barré syndrome (GBS). Antibodies against nerve gangliosides found in GBS patients recognize cross‐reactive epitopes in the lipopolysaccharide (LPS) of C. jejuni. This led to the molecular mimicry hypothesis of GBS. We immunized eleven rabbits with a LPS extracted from HS:19 C. jejuni strain isolated from a patient with GBS and complete Freund's adjuvant (CFA)(group I). In a second experiment we immunized seven rabbits with LPS, CFA and keyhole limpet hemocyanin (KLH)(group II). All group I rabbits developed high titers of anti‐LPS, anti‐GM1, anti‐GD1b antibodies and lower titers of anti‐GD1a. One rabbit, 50 days after initial inoculation, showed tremor and weakness. All rabbits of group II developed high titres of antiganglioside antibodies and six animals showed weakness 59–113 days after initial inoculation. Two rabbits died. Pathology showed mild to moderate, tendentially grouped, axonal degeneration in sciatic nerves of four out of five animals. Control rabbits of group I (immunized with CFA only) did not develop antibodies, controls of group II (immunized with CFA + KLH) developed low titers of IgG anti‐GM1. None developed neurological signs or showed axonal degeneration. C. jejuni LPS is a potent B‐cell stimulator capable to induce a strong antiganglioside response in rabbits. However, to induce the neuropathy is crucial to employ KLH, a glycoprotein known to stimulate both humoral and cellular responses. This animal model reproduces the pathogenetic process hypothesized in axonal GBS with antiganglioside antibodies post C. jejuni infection.     

Characterization of guanylate cyclase in squid photoreceptors

Light causes a rapid, 1.7-fold increase in cyclic GMP concentration in intact squid retinas (Johnson et al. (1986]. To determine whether light-induced changes in cyclic GMP concentration result from activation of guanylate cyclase, we have studied the regulation of guanylate cyclase activity in squid (Loligo pealei) photoreceptors. The enzyme is membrane-associated and activity is enhanced by the detergents Triton X-100 or digitonin. The enzyme requires divalent cations, Mn2+ being preferred over Mg2+. The dependence of enzyme activity on the MnGTP concentration deviates from simple Michaelis-Menten kinetics. Under conditions where a light-induced binding of GTP to the guanine nucleotide regulatory protein can be observed, no light-induced change in guanylate cyclase could be detected.     

Axonal transport and tissue contents of substance P in rats with long-term streptozotocin-diabetes. Effects of the aldose reductase inhibitor ‘statil’

This study examined the axonal transport of substance P-like immunoreactivity (SPLI) and its content in dorsal root ganglion, trigeminal ganglion, stomach and ileum of non-diabetic rats and two groups of rats with streptozotocin-induced diabetes of 9 months duration. One diabetic group received the aldose reductase inhibitor ‘Statil’ throughout the period of study. To reduce morbidity all diabetic animals were given twice-weekly injections of a long-acting insulin which restricted weight loss but did not prevent regular and severe hyperglycaemia. Axonal transport of SPLI was studied by measurement of accumulation at 12 h ligatures on the left sciatic nerve. There were no differences between the 3 groups either in the calculated anterograde and retrograde mean rates of accumulation (ranges 6.0 to 7.6 and 0.38 to 0.72 mm/h respectively) or mobile fractions of SPLI (means from 0.54 to 0.58). There were, however, marked reductions in anterograde and retrograde accumulations of SPLI in the constricted nerves of the ‘untreated’ diabetics (respectively 57 and 33% of controls;P < 0.01 for both). In the ‘Statil’-treated rats these deficits were attenuated (80 and 75% of controls). Diabetes also reduced the SPLI content of unligated sciatic nerve and trigeminal ganglion (65 and 75% of controls). ‘Statil’ prevented the deficit in the ganglion, but not in the nerve. ‘Statil’ treatment prevented themyo-inositol depletion and attenuated the sorbitol and fructose accumulation seen in the sciatic nerves of the untreated diabetic animals suggesting effective inhibition of aldose reductase in this tissue. The total SPLI content of the stomach and 1-cm segments of ileum were unaltered in the diabetic animals but due to the increased weights of these tissues the SPLI content per unit weight was reduced. These changes were unaffected by ‘Statil’.     

Low-dose doxorubicin in the management of advanced carcinoma of the prostate

Twenty-one patients with advanced metastatic carcinoma of the prostate, no longer responsive to conventional therapy, were treated with weekly low-dose doxorubicin (Adriamycin). Twelve had an impressive subjective response in terms of pain relief and improved performance status and in nine this was maintained for 3 or more months.     

Prospective study of the complications of endoscopic laryngeal surgery

Patients undergoing 204 endoscopic laryngeal operations were studied prospectively to determine the incidence of complications. Twelve patients were considered to be at high risk of postoperative airway obstruction. Two of these patients had an elective tracheostomy. One required temporary reintubation in the recovery room. No case of respiratory obstruction occurred in a patient not considered to be in the high risk group. Mucosal haemorrhage or oedema was seen on postoperative indirect laryngoscopy in 31 per cent of patients. The commonest abnormality found was mucosal haemorrhage in the oropharynx.